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Article(id=1320442415119450748, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1320442360509616480, articleNumber=null, orderNo=null, doi=10.16016/j.2097-0927.202602079, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1771084800000, receivedDateStr=2026-02-15, revisedDate=1773244800000, revisedDateStr=2026-03-12, acceptedDate=null, acceptedDateStr=null, onlineDate=1792747604398, onlineDateStr=2026-10-23, pubDate=1778774400000, pubDateStr=2026-05-15, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792747604398, onlineIssueDateStr=2026-10-23, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792747604398, creator=13701087609, updateTime=1792747604398, updator=13701087609, issue=Issue{id=1320442360509616480, tenantId=1146029695717560320, journalId=1319373162502258839, year='2026', volume='48', issue='9', pageStart='1129', pageEnd='1288', issueExtLink='null', onlineDate='null', pubDate='1778774400000', pubDateStr='2026-05-15', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1792747591378, creator='13701087609', updateTime=1792749835358, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1320451772548760069, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1320442360509616480, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1320451772548760070, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1320442360509616480, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1167, endPage=1180, ext={EN=ArticleExt(id=1320442415354331773, articleId=1320442415119450748, tenantId=1146029695717560320, journalId=1319373162502258839, language=EN, title=Alpha-2,3 sialylation promotes osteogenic and chondrogenic differentiation by regulating extracellular matrix homeostasis to participate in skeletal development, columnId=1320434418116837551, journalTitle=Journal of Army Medical University, columnName=Basic Medicine, runingTitle=null, highlight=null, articleAbstract=
Objective

Sialylation, an important post-translational modification, plays a key role in processes such as cell recognition and signal transduction. This study aims to explore the role of α-2,3 sialylation in osteogenic and chondrogenic differentiation, further elucidate its impact on bone development by regulating extracellular matrix (ECM) homeostasis, and provide novel theoretical basis and potential intervention targets for disorders of skeletal development.

Methods

The expression profiles of sialyltransferase family genes in osteogenic and chondrogenic differentiation were analyzed using public datasets GSE109503 (chondrogenic differentiation) and GSE113253 (osteogenic differentiation). In vitro differentiation experiments were conducted using MC3T3-E1 osteoblast and ATDC5 cells, and qRT-PCR was performed to screen for core differentially expressed genes (DEGs) in the sialyltransferase family (screening threshold |Log₂FC|>1, P<0.05). Stable α-2,3-type sialylation-deficient MC3T3-E1 and ATDC5 cells were constructed using lentiviral vectors, followed by osteogenic or chondrogenic induction for 7 and 14 d. Differentiation capacity was evaluated by ALP staining, Alizarin Red S staining, and Alcian blue staining. The expression of osteogenic marker genes (Col1a1, Sp7) and chondrogenic marker gene (Col2a1) was detected by qRT-PCR and Western blotting. Transcriptome sequencing was performed on α-2,3 sialylation-deficient MC3T3-E1 cells (osteogenic induction for 7 d) and ATDC5 cells (chondrogenic induction for 7 d), and biological functions of DEGs were analyzed with GO and KEGG enrichment analyses. For in vivo experiments, newborn C57BL/6 mice (half male and half female, body weight 1.0 to 1.5 g, on the day of birth) were randomly divided into 2 groups: an sialidase-treated group (intraperitoneally injected with sialidase, 0.2 U/dose, every other day for 4 weeks), and a control group (same volume of normal saline), with 6 animals in each group. Micro-CT scanning was conducted to analyze the bone microstructure parameters of the femur.

Results

Public dataset analysis revealed that only St3gal1 was significantly upregulated during both osteogenic and chondrogenic differentiation (|Log₂FC| >1, P<0.05). The in vitro cell differentiation model confirmed that St3gal1was significantly upregulated in both differentiation processes (P<0.000 1). Consistent with the public dataset transcriptome sequencing results, this demonstrated that St3gal1-mediated α-2,3-type sialylation accompanies the progression of osteogenic and chondrogenic differentiation. Following disruption of α-2,3 sialylation, ALP staining and Alizarin Red S staining in MC3T3-E1 cells were significantly attenuated, along with the mRNA expression levels of Col1a1and Sp7reduced to 60.7% (P<0.000 1) and 49% (P<0.000 1) of the control group, respectively, and corresponding protein levels decreasing to 61.5% (P=0.000 2) and 56.1% (P=0.000 3), respectively. In ATDC5 cells, Alcian Blue staining was markedly diminished, and CollagenⅡ protein expression was reduced to 43.1% of the control group (P<0.000 1). Transcriptomic sequencing results demonstrated that DEGs in both cell types were significantly enriched to ECM structure, and molecular functions were associated with ECM structural constituent. Pathway enrichment analyses revealed that DEGs were significantly enriched in ECM-receptor interaction and related signaling pathways (|Log₂FC|>1, FDR<0.05), suggesting that sialylation may regulate osteogenic and chondrogenic differentiation through multiple pathways, including ECM homeostasis, thereby contributing to bone development. In vivo experiments confirmed that, the sialidase-treated group exhibited reductions in femoral bone mineral density (decreased by 0.078 g/cm³, P<0.000 1), trabecular bone volume fraction (decreased by 5.512%, P<0.000 1), cortical thickness (decreased by 0.012 mm, P=0.001 1), trabecular number (decreased by 1.39/mm, P<0.000 1), and trabecular thickness (decreased by 0.002 3 mm, P=0.026 7), and an increase in trabecular separation (increased by 0.35 mm, P<0.000 1) when compared with the control group, indicating impaired skeletal development.

Conclusion

α-2,3 Sialylation positively regulates osteogenic and chondrogenic differentiation through modulating ECM homeostasis and plays an essential role in skeletal development. Sialylation within the bone microenvironment may serve as a potential intervention target for skeletal dysplasia disorders.

, authors=Dongyang ZHANG, Yong TANG, Jiulin TAN, Qijie DAI, Jianzhong XU, Ce DOU, authorsList=Dongyang ZHANG, Yong TANG, Jiulin TAN, Qijie DAI, Jianzhong XU, Ce DOU, authorCompany=null, correspAuthors=Jianzhong XU, Ce DOU, authorNote=null, correspAuthorsNote=null, copyrightStatement=© 2026 Journal of Army Medical University, copyrightOwner=Editorial Office of Journal of Army Medical University, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1320442418588140172, articleId=1320442415119450748, tenantId=1146029695717560320, journalId=1319373162502258839, language=CN, title=α-2，3型唾液酸化修饰通过调控细胞外基质稳态促进成骨与成软骨分化参与骨骼发育, columnId=1320434418343329969, journalTitle=陆军军医大学学报, columnName=论著·基础医学, runingTitle=null, highlight=null, articleAbstract=
目的

唾液酸化修饰作为一种重要的翻译后修饰，在细胞识别、信号转导等过程中发挥关键作用，通过探究α-2，3型唾液酸化修饰在成骨与成软骨分化过程中的作用，进一步明确其通过调控细胞外基质稳态对骨发育进程的影响，为骨骼发育障碍等疾病提供新的理论依据和潜在干预靶点。

方法

通过公共数据集GSE109503（成软骨分化）和GSE113253（成骨分化）分析唾液酸转移酶家族基因在成软骨与成骨分化中的表达谱，结合MC3T3-E1成骨细胞和ATDC5成软骨细胞模型进行体外分化实验进行qRT-PCR检测，筛选唾液酸转移酶家族核心差异基因（筛选阈值|Log₂FC|>1，P<0.05）。利用慢病毒构建稳定的α-2，3型唾液酸化修饰缺陷的MC3T3-E1成骨细胞和ATDC5成软骨细胞模型，分别进行成骨或成软骨诱导7、14 d，通过ALP染色、茜素红S染色、阿尔辛蓝染色观察分化能力，荧光定量PCR和Western blotting检测成骨标志基因（Col1a1、Sp7）和软骨标志基因（Col2a1）以及蛋白的表达。对α-2，3型唾液酸化修饰缺陷的MC3T3-E1细胞（成骨诱导7 d）和ATDC5细胞（成软骨诱导7 d）进行转录组测序，通过GO和KEGG富集分析解析差异基因的生物学功能。体内实验选取新生C57BL/6小鼠（雌雄各半，体质量1.0~1.5 g，出生当日），所有小鼠按随机数字表法分为（n=6）：唾液酸酶处理组［腹腔注射唾液酸酶（0.2 U/次，隔天1次，持续4周）］和对照组（注射等体积生理盐水）；采用Micro-CT分析股骨骨微结构参数。

结果

公共数据集显示仅St3gal1在成骨与成软骨分化中均显著上调（|Log₂FC|>1，P<0.05）；细胞体外分化模型验证了St3gal1在两种分化过程中均显著上调（P<0.000 1）。与公共数据集转录组测序结果相一致，证明了St3gal1介导的α-2，3型唾液酸化修饰伴随成骨与成软骨的分化进程。干扰α-2，3型唾液酸化修饰后，MC3T3-E1细胞ALP染色和茜素红S染色显著减弱，Col1a1和Sp7的mRNA表达分别降至对照组的60.7%（P<0.000 1）和49%（P<0.000 1）；蛋白水平同步降低，分别降至对照组的61.5%（P=0.000 2）和56.1%（P=0.000 3）；ATDC5细胞阿尔辛蓝染色显著减弱，Collagen Ⅱ蛋白表达降至对照组的43.1%（P<0.000 1）。转录组测序结果显示，差异基因在2组细胞中均显著定位于细胞外基质结构，分子功能均与细胞外基质结构组成相关；通路富集分析显示，差异基因均显著富集于ECM-受体互作等相关信号通路，提示唾液酸化修饰可能通过细胞外基质稳态等多条信号通路调控成骨与成软骨分化进而参与骨发育进程（|Log₂FC|>1，FDR<0.05）。体内实验证实，与对照组相比，唾液酸酶处理组小鼠股骨骨密度下降0.078 g/cm3（P<0.000 1）、骨小梁体积分数下降5.512%（P<0.000 1）、皮质骨厚度下降0.012 mm（P=0.001 1）及骨小梁数量下降1.39/mm（P<0.000 1）、骨小梁厚度下降0.002 3 mm（P=0.026 7）、骨小梁分离度增加0.35 mm（P<0.000 1），提示骨骼发育异常。

结论

α-2，3型唾液酸化修饰通过调控细胞外基质稳态正向调节成骨与成软骨分化，在骨骼发育中发挥关键作用。骨微环境中唾液酸化修饰可能成为骨骼发育不良性疾病的潜在干预靶点。

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许建中，E-mail：
窦策，E-mail：
XU Jianzhong，E-mail：
DOU Ce，E-mail：
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tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1038/s41574-024-00969-x, pmid=null, pmcid=null, year=2024, volume=20, issue=7, pageStart=399, pageEnd=413, url=null, language=null, rfNumber=1, rfOrder=0, authorNames=STEGEN S, CARMELIET G, journalName=Nat Rev Endocrinol, refType=null, unstructuredReference=STEGEN S， CARMELIET G. Metabolic regulation of skeletal cell fate and function［J］. Nat Rev Endocrinol， 2024， 20（7）： 399-413., articleTitle=Metabolic regulation of skeletal cell fate and function, refAbstract=null), Reference(id=1320442426460848841, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1093/procel/pwae008, pmid=null, pmcid=null, year=2024, volume=15, issue=8, pageStart=559, pageEnd=574, url=null, language=null, rfNumber=2, rfOrder=1, authorNames=YUAN G X, LIN X X, LIU Y, journalName=Protein Cell, refType=null, unstructuredReference=YUAN G X， LIN X X， LIU Y， et al. Skeletal stem cells in bone development， homeostasis， and disease［J］. Protein Cell， 2024， 15（8）： 559-574., articleTitle=Skeletal stem cells in bone development， homeostasis， and disease, refAbstract=null), Reference(id=1320442426532152010, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1093/jbmr/zjae069, pmid=null, pmcid=null, year=2024, volume=39, issue=6, pageStart=633, pageEnd=654, url=null, language=null, rfNumber=3, rfOrder=2, authorNames=TROMPET D, MELIS S, CHAGIN A S, journalName=J Bone Miner Res, refType=null, unstructuredReference=TROMPET D， MELIS S， CHAGIN A S， et al. Skeletal stem and progenitor cells in bone development and repair［J］. J Bone Miner Res， 2024， 39（6）： 633-654., articleTitle=Skeletal stem and progenitor cells in bone development and repair, refAbstract=null), Reference(id=1320442426599260875, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1146/annurev.cellbio.16.1.191, pmid=null, pmcid=null, year=2000, volume=16, issue=null, pageStart=191, pageEnd=220, url=null, language=null, rfNumber=4, rfOrder=3, authorNames=OLSEN B R, REGINATO A M, WANG W F, journalName=Annu Rev Cell Dev Biol, refType=null, unstructuredReference=OLSEN B R， REGINATO A M， WANG W F. Bone development［J］. Annu Rev Cell Dev Biol， 2000， 16： 191-220., articleTitle=Bone development, refAbstract=null), Reference(id=1320442426687341260, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1038/s41467-024-49203-2, pmid=null, pmcid=null, year=2024, volume=15, issue=1, pageStart=4820, pageEnd=null, url=null, language=null, rfNumber=5, rfOrder=4, authorNames=DARBELLAY F, RAMISCH A, LOPEZ-DELISLE L, journalName=Nat Commun, refType=null, unstructuredReference=DARBELLAY F， RAMISCH A， LOPEZ-DELISLE L， et al. Pre-hypertrophic chondrogenic enhancer landscape of limb and axial skeleton development［J］. Nat Commun， 2024， 15（1）： 4820., articleTitle=Pre-hypertrophic chondrogenic enhancer landscape of limb and axial skeleton development, refAbstract=null), Reference(id=1320442426783810253, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1007/s10555-021-10015-1, pmid=null, pmcid=null, year=2022, volume=41, issue=1, pageStart=107, pageEnd=129, url=null, language=null, rfNumber=6, rfOrder=5, authorNames=BINDEMAN W E, FINGLETON B, journalName=Cancer Metastasis Rev, refType=null, unstructuredReference=BINDEMAN W E， FINGLETON B. Glycosylation as a regulator of site-specific metastasis［J］. Cancer Metastasis Rev， 2022， 41（1）： 107-129., articleTitle=Glycosylation as a regulator of site-specific metastasis, refAbstract=null), Reference(id=1320442426850919118, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=null, pmid=null, pmcid=null, year=2011, volume=23, issue=7, pageStart=678, pageEnd=684, url=null, language=null, rfNumber=7, rfOrder=6, authorNames=张嘉宁, 汪淑晶, journalName=生命科学, refType=null, unstructuredReference=张嘉宁， 汪淑晶. 唾液酸生物学与人类健康和疾病［J］. 生命科学， 2011， 23（7）： 678-684., articleTitle=唾液酸生物学与人类健康和疾病, refAbstract=null), Reference(id=1320442426959971023, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=null, pmid=null, pmcid=null, year=2011, volume=23, issue=7, pageStart=678, pageEnd=684, url=null, language=null, rfNumber=7, rfOrder=7, authorNames=ZHANG J N, WANG S J, journalName=Chin Bull Life Sci, refType=null, unstructuredReference=ZHANG J N， WANG S J. Sialobiology in human health and disease［J］. Chin Bull Life Sci， 2011， 23（7）： 678-684., articleTitle=Sialobiology in human health and disease, refAbstract=null), Reference(id=1320442427035468496, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1021/acs.chemrev.1c01032, pmid=null, pmcid=null, year=2022, volume=122, issue=20, pageStart=15603, pageEnd=15671, url=null, language=null, rfNumber=8, rfOrder=8, authorNames=SHIVATARE S S, SHIVATARE V S, WONG C H, journalName=Chem Rev, refType=null, unstructuredReference=SHIVATARE S S， SHIVATARE V S， WONG C H. Glycoconjugates： synthesis， functional studies， and therapeutic developments［J］. Chem Rev， 2022， 122（20）： 15603-15671., articleTitle=Glycoconjugates： synthesis， functional studies， and therapeutic developments, refAbstract=null), Reference(id=1320442427127743185, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.12354/j.issn.1000-8179.2025.20241623, pmid=null, pmcid=null, year=2025, volume=52, issue=2, pageStart=81, pageEnd=85, url=null, language=null, rfNumber=9, rfOrder=9, authorNames=许青, 段嘉蓉, 郑天清, journalName=中国肿瘤临床, refType=null, unstructuredReference=许青， 段嘉蓉， 郑天清. 靶向唾液酸-Siglec在肿瘤免疫治疗中的研究进展［J］. 中国肿瘤临床， 2025， 52（2）： 81-85., articleTitle=靶向唾液酸-Siglec在肿瘤免疫治疗中的研究进展, refAbstract=null), Reference(id=1320442427207434962, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.12354/j.issn.1000-8179.2025.20241623, pmid=null, pmcid=null, year=2025, volume=52, issue=2, pageStart=81, pageEnd=85, url=null, language=null, rfNumber=9, rfOrder=10, authorNames=XU Q, DUAN J R, ZHENG T Q, journalName=Chin J Clin Oncol, refType=null, unstructuredReference=XU Q， DUAN J R， ZHENG T Q. Research progress on tumor immunotherapy targeting sialic acid-Siglec complexes［J］. Chin J Clin Oncol， 2025， 52（2）： 81-85., articleTitle=Research progress on tumor immunotherapy targeting sialic acid-Siglec complexes, refAbstract=null), Reference(id=1320442427278738131, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1186/s40035-025-00506-4, pmid=null, pmcid=null, year=2025, volume=14, issue=1, pageStart=47, pageEnd=null, url=null, language=null, rfNumber=10, rfOrder=11, authorNames=CHENG S L, XIAO B, LUO Z H, journalName=Transl Neurodegener, refType=null, unstructuredReference=CHENG S L， XIAO B， LUO Z H. Glycosylation in neuroinflammation： mechanisms， implications， and therapeutic strategies for neurodegenerative diseases［J］. Transl Neurodegener， 2025， 14（1）： 47., articleTitle=Glycosylation in neuroinflammation： mechanisms， implications， and therapeutic strategies for neurodegenerative diseases, refAbstract=null), Reference(id=1320442427358429908, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1073/pnas.2411600122, pmid=null, pmcid=null, year=2025, volume=122, issue=20, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=11, rfOrder=12, authorNames=SNEED S L, STRANDBERG E A, LAUREANO A F S, journalName=Proc Natl Acad Sci U S A, refType=null, unstructuredReference=SNEED S L， STRANDBERG E A， LAUREANO A F S， et al. Molecular determinants of sialylated IgG anti-inflammatory activity［J］. Proc Natl Acad Sci U S A， 2025， 122（20）： e2411600122., articleTitle=Molecular determinants of sialylated IgG anti-inflammatory activity, refAbstract=null), Reference(id=1320442427433927381, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1038/s41413-023-00293-6, pmid=null, pmcid=null, year=2023, volume=11, issue=1, pageStart=55, pageEnd=null, url=null, language=null, rfNumber=12, rfOrder=13, authorNames=YANG S F, HE Z Y, WU T, journalName=Bone Res, refType=null, unstructuredReference=YANG S F， HE Z Y， WU T， et al. Glycobiology in osteoclast differentiation and function［J］. Bone Res， 2023， 11（1）： 55., articleTitle=Glycobiology in osteoclast differentiation and function, refAbstract=null), Reference(id=1320442427509424854, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1038/s41413-022-00186-0, pmid=null, pmcid=null, year=2022, volume=10, issue=1, pageStart=24, pageEnd=null, url=null, language=null, rfNumber=13, rfOrder=14, authorNames=DOU C, ZHEN G H, DAN Y, journalName=Bone Res, refType=null, unstructuredReference=DOU C， ZHEN G H， DAN Y， et al. Sialylation of TLR2 initiates osteoclast fusion［J］. Bone Res， 2022， 10（1）： 24., articleTitle=Sialylation of TLR2 initiates osteoclast fusion, refAbstract=null), Reference(id=1320442427643642583, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1016/s1074-7613（00）80180-6, pmid=null, pmcid=null, year=2000, volume=12, issue=3, pageStart=273, pageEnd=283, url=null, language=null, rfNumber=14, rfOrder=15, authorNames=PRIATEL J J, CHUI D, HIRAOKA N, journalName=Immunity, refType=null, unstructuredReference=PRIATEL J J， CHUI D， HIRAOKA N， et al. The ST3Gal-I sialyltransferase controls CD8+ T lymphocyte homeostasis by modulating O-glycan biosynthesis［J］. Immunity， 2000， 12（3）： 273-283., articleTitle=The ST3Gal-I sialyltransferase controls CD8+ T lymphocyte homeostasis by modulating O-glycan biosynthesis, refAbstract=null), Reference(id=1320442427731722968, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1016/j.carres.2024.109242, pmid=null, pmcid=null, year=2024, volume=544, issue=null, pageStart=109242, pageEnd=null, url=null, language=null, rfNumber=15, rfOrder=16, authorNames=MOHAMED K A, KRUF S, BÜLL C, journalName=Carbohydr Res, refType=null, unstructuredReference=MOHAMED K A， KRUF S， BÜLL C. Putting a cap on the glycome： Dissecting human sialyltransferase functions［J］. Carbohydr Res， 2024， 544： 109242., articleTitle=Putting a cap on the glycome： Dissecting human sialyltransferase functions, refAbstract=null), Reference(id=1320442427811414745, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1158/2326-6066.CIR-20-0203, pmid=null, pmcid=null, year=2021, volume=9, issue=1, pageStart=113, pageEnd=122, url=null, language=null, rfNumber=16, rfOrder=17, authorNames=LIN W D, FAN T C, HUNG J T, journalName=Cancer Immunol Res, refType=null, unstructuredReference=LIN W D， FAN T C， HUNG J T， et al. Sialylation of CD55 by ST3GAL1 facilitates immune evasion in cancer［J］. Cancer Immunol Res， 2021， 9（1）： 113-122., articleTitle=Sialylation of CD55 by ST3GAL1 facilitates immune evasion in cancer, refAbstract=null), Reference(id=1320442427886912218, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.13423/j.cnki.cjcmi.009945, pmid=null, pmcid=null, year=2025, volume=41, issue=4, pageStart=308, pageEnd=317, url=null, language=null, rfNumber=17, rfOrder=18, authorNames=赵自豪, 郑文静, 张玲玲, journalName=细胞与分子免疫学杂志, refType=null, unstructuredReference=赵自豪， 郑文静， 张玲玲， 等. 唾液酸转移酶ST3GAL1促进胶质瘤恶性进展［J］. 细胞与分子免疫学杂志， 2025， 41（4）： 308-317., articleTitle=唾液酸转移酶ST3GAL1促进胶质瘤恶性进展, refAbstract=null), Reference(id=1320442427991769819, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.13423/j.cnki.cjcmi.009945, pmid=null, pmcid=null, year=2025, volume=41, issue=4, pageStart=308, pageEnd=317, url=null, language=null, rfNumber=17, rfOrder=19, authorNames=ZHAO Z H, ZHENG W J, ZHANG L L, journalName=Chin J Cell Mol Immunol, refType=null, unstructuredReference=ZHAO Z H， ZHENG W J， ZHANG L L， et al. Sialyltransferase ST3GAL1 promotes malignant progression in glioma［J］. Chin J Cell Mol Immunol， 2025， 41（4）： 308-317., articleTitle=Sialyltransferase ST3GAL1 promotes malignant progression in glioma, refAbstract=null), Reference(id=1320442428100821724, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1146/annurev-cellbio-100109-104020, pmid=null, pmcid=null, year=2010, volume=26, issue=null, pageStart=397, pageEnd=419, url=null, language=null, rfNumber=18, rfOrder=20, authorNames=SINGH P, CARRAHER C, SCHWARZBAUER J E, journalName=Annu Rev Cell Dev Biol, refType=null, unstructuredReference=SINGH P， CARRAHER C， SCHWARZBAUER J E. Assembly of fibronectin extracellular matrix［J］. Annu Rev Cell Dev Biol， 2010， 26： 397-419., articleTitle=Assembly of fibronectin extracellular matrix, refAbstract=null), Reference(id=1320442428209873629, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1016/j.bpj.2010.03.063, pmid=null, pmcid=null, year=2010, volume=99, issue=1, pageStart=208, pageEnd=217, url=null, language=null, rfNumber=19, rfOrder=21, authorNames=PAN D, SONG Y H, journalName=Biophys J, refType=null, unstructuredReference=PAN D， SONG Y H. Role of altered sialylation of the I-like domain of beta1 integrin in the binding of fibronectin to beta1 integrin： thermodynamics and conformational analyses［J］. Biophys J， 2010， 99（1）： 208-217., articleTitle=Role of altered sialylation of the I-like domain of beta1 integrin in the binding of fibronectin to beta1 integrin： thermodynamics and conformational analyses, refAbstract=null), Reference(id=1320442428314731230, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.7518/hxkq.2023.2023055, pmid=null, pmcid=null, year=2023, volume=41, issue=4, pageStart=395, pageEnd=404, url=null, language=null, rfNumber=20, rfOrder=22, authorNames=郑雯, 蔡明详, 彭荟桢, journalName=华西口腔医学杂志, refType=null, unstructuredReference=郑雯， 蔡明详， 彭荟桢， 等. 不同硫酸化程度的糖胺聚糖成软骨作用的体外研究［J］. 华西口腔医学杂志， 2023， 41（4）： 395-404., articleTitle=不同硫酸化程度的糖胺聚糖成软骨作用的体外研究, refAbstract=null), Reference(id=1320442428394423007, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.7518/hxkq.2023.2023055, pmid=null, pmcid=null, year=2023, volume=41, issue=4, pageStart=395, pageEnd=404, url=null, language=null, rfNumber=20, rfOrder=23, authorNames=ZHENG W, CAI M X, PENG H Z, journalName=West China J Stomatol, refType=null, unstructuredReference=ZHENG W， CAI M X， PENG H Z， et al. Effect of glycosaminoglycans with different degrees of sulfation on chondrogenesis［J］. West China J Stomatol， 2023， 41（4）： 395-404., articleTitle=Effect of glycosaminoglycans with different degrees of sulfation on chondrogenesis, refAbstract=null), Reference(id=1320442428620915424, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1053/sarh.2000.24874, pmid=null, pmcid=null, year=2001, volume=31, issue=1, pageStart=58, pageEnd=68, url=null, language=null, rfNumber=21, rfOrder=24, authorNames=BALI J P, COUSSE H, NEUZIL E, journalName=Semin Arthritis Rheum, refType=null, unstructuredReference=BALI J P， COUSSE H， NEUZIL E. Biochemical basis of the pharmacologic action of chondroitin sulfates on the osteoarticular system［J］. Semin Arthritis Rheum， 2001， 31（1）： 58-68., articleTitle=Biochemical basis of the pharmacologic action of chondroitin sulfates on the osteoarticular system, refAbstract=null), Reference(id=1320442428721578721, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1002/anie.202525026, pmid=null, pmcid=null, year=2026, volume=65, issue=9, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=22, rfOrder=25, authorNames=WU Y, MA W J, JIANG Y Y, journalName=Angew Chem Int Ed, refType=null, unstructuredReference=WU Y， MA W J， JIANG Y Y， et al. Chemoenzymatic synthesis of glycopeptide library Decodes Sialylation-dependent immunodominance to enable a potent multicomponent antitumor vaccine［J］. Angew Chem Int Ed， 2026， 65（9）： e25026., articleTitle=Chemoenzymatic synthesis of glycopeptide library Decodes Sialylation-dependent immunodominance to enable a potent multicomponent antitumor vaccine, refAbstract=null), Reference(id=1320442429044540130, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1126/sciadv.adu3739, pmid=null, pmcid=null, year=2025, volume=11, issue=27, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=23, rfOrder=26, authorNames=FUCHS A L, SINGH B, JETMORE J W, journalName=Sci Adv, refType=null, unstructuredReference=FUCHS A L， SINGH B， JETMORE J W， et al. Mitochondrial dysfunction enhances influenza pathogenesis by up-regulating de novo sialic acid biosynthesis［J］. Sci Adv， 2025， 11（27）： eadu3739., articleTitle=Mitochondrial dysfunction enhances influenza pathogenesis by up-regulating de novo sialic acid biosynthesis, refAbstract=null), Reference(id=1320442429161980643, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1016/j.redox.2025.103901, pmid=null, pmcid=null, year=2025, volume=88, issue=null, pageStart=103901, pageEnd=null, url=null, language=null, rfNumber=24, rfOrder=27, authorNames=WANG X, LIU H, YUE M W, journalName=Redox Biol, refType=null, unstructuredReference=WANG X， LIU H， YUE M W， et al. Nitrate maintains mitochondrial membrane integrity by increasing Sialin-FKBP8 granules via liquid-liquid-phase separation［J］. Redox Biol， 2025， 88： 103901., articleTitle=Nitrate maintains mitochondrial membrane integrity by increasing Sialin-FKBP8 granules via liquid-liquid-phase separation, refAbstract=null), Reference(id=1320442429552050916, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=null, pmid=null, pmcid=null, year=1996, volume=74, issue=5, pageStart=907, pageEnd=920, url=null, language=null, rfNumber=25, rfOrder=28, authorNames=GELBERG H, HEALY L, WHITELEY H, journalName=Lab Invest, refType=null, unstructuredReference=GELBERG H， HEALY L， WHITELEY H， et al. In vivo enzymatic removal of alpha 2： >6-linked sialic acid from the glomerular filtration barrier results in podocyte charge alteration and glomerular injury［J］. Lab Invest， 1996， 74（5）： 907-920., articleTitle=In vivo enzymatic removal of alpha 2： >6-linked sialic acid from the glomerular filtration barrier results in podocyte charge alteration and glomerular injury, refAbstract=null), Reference(id=1320442429958898405, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1111/j.1365-2141.1972.tb08790.x, pmid=null, pmcid=null, year=1972, volume=22, issue=1, pageStart=93, pageEnd=101, url=null, language=null, rfNumber=26, rfOrder=29, authorNames=CHOI S I, SIMONE J V, JORNEY L J, journalName=Br J Haematol, refType=null, unstructuredReference=CHOI S I， SIMONE J V， JORNEY L J. Neuraminidase-induced thrombocytopenia in rats［J］. Br J Haematol， 1972， 22（1）： 93-101., articleTitle=Neuraminidase-induced thrombocytopenia in rats, refAbstract=null), Reference(id=1320442430365745894, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=null, pmid=null, pmcid=null, year=1978, volume=34, issue=3, pageStart=555, pageEnd=563, url=null, language=null, rfNumber=27, rfOrder=30, authorNames=KNOP J, AX W, SEDLACEK H H, journalName=Immunology, refType=null, unstructuredReference=KNOP J， AX W， SEDLACEK H H， et al. Effect of Vibriocholerae neuraminidase on the phagocytosis of E. coli by macrophages in vivo and in vitro［J］. Immunology， 1978， 34（3）： 555-563., articleTitle=Effect of Vibriocholerae neuraminidase on the phagocytosis of E. coli by macrophages in vivo and in vitro, refAbstract=null), Reference(id=1320442432341263079, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, doi=10.1016/j.jbc.2024.107450, pmid=null, pmcid=null, year=2024, volume=300, issue=7, pageStart=107450, pageEnd=null, url=null, language=null, rfNumber=28, rfOrder=31, authorNames=TOKORO Y, NAGAE M, NAKANO M, journalName=J Biol Chem, refType=null, unstructuredReference=TOKORO Y， NAGAE M， NAKANO M， et al. LacdiNAc synthase B4GALNT3 has a unique PA14 domain and suppresses N-glycan capping［J］. J Biol Chem， 2024， 300（7）： 107450., articleTitle=LacdiNAc synthase B4GALNT3 has a unique PA14 domain and suppresses N-glycan capping, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1320442418802049677, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, xref=1, ext=[AuthorCompanyExt(id=1320442418810438286, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, companyId=1320442418802049677, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Orthopedics， First Affiliated Hospital， Army Medical University （Third Military Medical University）， Chongqing， China), AuthorCompanyExt(id=1320442418814632591, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, companyId=1320442418802049677, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（第三军医大学）第一附属医院骨科，重庆)])], figs=[ArticleFig(id=1320442422992159416, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=EN, label=Figure 1, caption=Identification of the core differential genes of sialyltransferase family in osteogenic and chondrogenic differentiation, figureFileSmall=m1cHHarRz6HJZTxOcW1H3g==, figureFileBig=fdH2dr00EzFJJ94N4I2zTQ==, tableContent=null), ArticleFig(id=1320442423155737273, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=CN, label=图1, caption=鉴定成骨和成软骨分化中唾液酸转移酶家族的核心差异基因

A： Volcano plots showing the expression changes in sialyltransferase family genes in the GSE109503 （chondrogenic differentiation） and GSE113253 （osteogenic differentiation） datasets； B： Box plots showing the sample expression distribution of the control group and the induction group in the above 2 datasets； C： Venn diagram showing the intersection of sialyltransferase family genes that are expressed in both datasets； D and E： Relative mRNA expression levels of core differentially expressed genes （DEGs） in the sialyltransferase family at days 0， 7 and 14 of osteogenic and chondrogenic differentiation （n=3， x¯±s）

, figureFileSmall=m1cHHarRz6HJZTxOcW1H3g==, figureFileBig=fdH2dr00EzFJJ94N4I2zTQ==, tableContent=null), ArticleFig(id=1320442423386423994, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=EN, label=Figure 2, caption=Effects of α-2，3 sialylation defects on osteogenic differentiation of MC3T3-E1 cells（n=3， x¯±s）, figureFileSmall=bkkTy/f8l1vT8jEu5yjG0Q==, figureFileBig=e4vcGf2/UayTzue+mGv/Tw==, tableContent=null), ArticleFig(id=1320442423583556283, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=CN, label=图2, caption=α-2，3型唾液酸化修饰缺陷对MC3T3-E1细胞成骨分化的影响（n=3， x¯±s）

A： Knockout efficiency of St3gal1 in each group detected by qRT-PCR and immunofluorescence （blue： DAPI； green： ST3GAL1）； B： ALP staining and analysis of early osteogenic differentiation in MC3T3-E1 cells； C： Alizarin Red S staining and detection of mineralized nodule formation in MC3T3-E1 cells

, figureFileSmall=bkkTy/f8l1vT8jEu5yjG0Q==, figureFileBig=e4vcGf2/UayTzue+mGv/Tw==, tableContent=null), ArticleFig(id=1320442423663248060, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=EN, label=Figure 3, caption=Defect of α-2，3 sialylation modification interferes with osteogenic differentiation by regulating extracellular matrix （ECM） homeostasis, figureFileSmall=WQLC9pooOVUK/HtXMDBrvw==, figureFileBig=+1y9Tti9/ZUQiUc6dkKXoA==, tableContent=null), ArticleFig(id=1320442423742939837, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=CN, label=图3, caption=α-2，3型唾液酸化修饰缺陷通过调控细胞外基质稳态干扰成骨分化进程

A： Heatmap of differentially expressed genes； B： Volcano plot of differential expression； C to E： Results of GO enrichment analysis； F： Results of KEGG pathway enrichment analysis

, figureFileSmall=WQLC9pooOVUK/HtXMDBrvw==, figureFileBig=+1y9Tti9/ZUQiUc6dkKXoA==, tableContent=null), ArticleFig(id=1320442423881351870, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=EN, label=Figure 4, caption=α-2，3 sialylation regulates the expression of key matrix proteins and osteogenic transcription, figureFileSmall=TP45XpEYy6/vTgB9Pngb9w==, figureFileBig=cNpC3rostlF+RAr5Xqeu6g==, tableContent=null), ArticleFig(id=1320442424011375295, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=CN, label=图4, caption=α-2，3型唾液酸化修饰对成骨关键基质蛋白及成骨转录因子的表达调控（n=3， x¯±s）

A： Differentially expressed osteogenesis-related genes as shown by transcriptome sequencing； B： Verification of the expression of key osteogenic differentiation-related genes by qRT-PCR； C： Representative images of Western blotting and statistical results of expression levels of osteogenesis-related proteins

, figureFileSmall=TP45XpEYy6/vTgB9Pngb9w==, figureFileBig=cNpC3rostlF+RAr5Xqeu6g==, tableContent=null), ArticleFig(id=1320442424099455680, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=EN, label=Figure 5, caption=Effect of α-2，3 sialylation modification on cartilage matrix synthesis during chondrogenic differentiation, figureFileSmall=jbtL+Yb9AXz+6iKIaaoYNQ==, figureFileBig=p+YCWM8rN7UfIvlPRUqqEA==, tableContent=null), ArticleFig(id=1320442424435000001, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=CN, label=图5, caption=干扰α-2，3型唾液酸化修饰对ATDC5细胞成软骨分化进程中软骨基质合成能力的影响（n=3， x¯±s）

A： Knockout efficiency of St3gal1 in each group detected by qRT-PCR and immunofluorescence （blue： DAPI； green： ST3GAL1）； B： Alcian Blue staining for chondrogenic differentiation in ATDC5 cells； C： Representative images of Western blotting of chondrogenesis-related protein expression levels

, figureFileSmall=jbtL+Yb9AXz+6iKIaaoYNQ==, figureFileBig=p+YCWM8rN7UfIvlPRUqqEA==, tableContent=null), ArticleFig(id=1320442424506303170, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=EN, label=Figure 6, caption=Defect of α-2，3 sialylation modification participants in chondrogenic differentiation in ATDC5 cells by regulating ECM homeostasis, figureFileSmall=RpYdAlk8AUNgHFG8ip548g==, figureFileBig=KG2zATLuBjHZ9MUs58dxWA==, tableContent=null), ArticleFig(id=1320442424833458883, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=CN, label=图6, caption=α-2，3型唾液酸化修饰缺陷通过调控细胞外基质稳态参与软骨分化进程

A： Heatmap of differentially expressed genes； B： Volcano plot of differential expression； C and D： GO enrichment and KEGG pathway enrichment analyses

, figureFileSmall=RpYdAlk8AUNgHFG8ip548g==, figureFileBig=KG2zATLuBjHZ9MUs58dxWA==, tableContent=null), ArticleFig(id=1320442426028835524, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=EN, label=Figure 7, caption=Micro-CT analysis of growth plate and bone tissue development in the femurs of neonatal mice after 4 weeks, figureFileSmall=OLnk3jiWcMxYZfNrEZ8iUA==, figureFileBig=X3pyPSaWqZawLCLH92tAlg==, tableContent=null), ArticleFig(id=1320442426142081733, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=CN, label=图7, caption=Micro-CT分析唾液酸酶处理4周后新生小鼠股骨的生长板及骨组织发育结果（n=6， x¯±s）

A： Representative micro-CT images； B： Statistical results of micro-CT parameters； C： Comparison of sialic acid fluorescence intensity in the femoral tissue of mice （blue： DAPI； green： sialic acid）

, figureFileSmall=OLnk3jiWcMxYZfNrEZ8iUA==, figureFileBig=X3pyPSaWqZawLCLH92tAlg==, tableContent=null), ArticleFig(id=1320442426209190598, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=EN, label=Table 1, caption=

Primer sequences for qRT-PCR

, figureFileSmall=null, figureFileBig=null, tableContent=
Gene namePrimer sequence（5'→3'）
St3gal1Forward： TCCAACACGGGAGTACCCA
Reverse： GCTGGTCGAACCAATATGATACC
Col1a1Forward： TTGGTCGATGCAGCATAG
Reverse： CCGTAATTTTCCCGTATGCA
Sp7Forward： AAGTCTCAAGGTTATAGGGACGG
Reverse： CCATGCTTGTCTGGGTATAGTGT
Col2a1Forward： GGGTCACAGAGGTTACCCAG
Reverse： ACCAGGGGAACCACTCTCAC
St3gal2Forward： CTGCTCTTCACCTACTCGCAC
Reverse： GCTGTAGTCCTGAATAGCCTGG
St3gal4Forward： CCTCTAAGATTTTTGGCAACCGT
Reverse： CATAGGTGGATGGCGTCTTTAC
St6gal1Forward： TGTTTGCCATCATCTGCGTGT
Reverse： TCCTTAGGGTCTTGTTTGCTGT
GAPDHForward： AACGTCGGAACGATAGCA
Reverse： CTTAAGGCTAGTTAGGCCC
), ArticleFig(id=1320442426263716551, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320442415119450748, language=CN, label=表1, caption=

荧光定量PCR所用引物序列

, figureFileSmall=null, figureFileBig=null, tableContent=
Gene namePrimer sequence（5'→3'）
St3gal1Forward： TCCAACACGGGAGTACCCA
Reverse： GCTGGTCGAACCAATATGATACC
Col1a1Forward： TTGGTCGATGCAGCATAG
Reverse： CCGTAATTTTCCCGTATGCA
Sp7Forward： AAGTCTCAAGGTTATAGGGACGG
Reverse： CCATGCTTGTCTGGGTATAGTGT
Col2a1Forward： GGGTCACAGAGGTTACCCAG
Reverse： ACCAGGGGAACCACTCTCAC
St3gal2Forward： CTGCTCTTCACCTACTCGCAC
Reverse： GCTGTAGTCCTGAATAGCCTGG
St3gal4Forward： CCTCTAAGATTTTTGGCAACCGT
Reverse： CATAGGTGGATGGCGTCTTTAC
St6gal1Forward： TGTTTGCCATCATCTGCGTGT
Reverse： TCCTTAGGGTCTTGTTTGCTGT
GAPDHForward： AACGTCGGAACGATAGCA
Reverse： CTTAAGGCTAGTTAGGCCC
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α-2，3型唾液酸化修饰通过调控细胞外基质稳态促进成骨与成软骨分化参与骨骼发育
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张东阳 , 汤勇 , 谭玖琳 , 代其杰 , 许建中 , 窦策
陆军军医大学学报 | 论著·基础医学 2026,48(9): 1167-1180
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陆军军医大学学报 |论著·基础医学 2026 , 48 (9) : 1167 -1180
α-2，3型唾液酸化修饰通过调控细胞外基质稳态促进成骨与成软骨分化参与骨骼发育
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张东阳, 汤勇, 谭玖琳, 代其杰, 许建中 , 窦策
作者信息
  • 1陆军军医大学（第三军医大学）第一附属医院骨科，重庆
通讯作者:
许建中，E-mail：
窦策，E-mail：
XU Jianzhong，E-mail：
DOU Ce，E-mail：
Alpha-2,3 sialylation promotes osteogenic and chondrogenic differentiation by regulating extracellular matrix homeostasis to participate in skeletal development
Dongyang ZHANG, Yong TANG, Jiulin TAN, Qijie DAI, Jianzhong XU , Ce DOU
Affiliations
  • 1Department of Orthopedics， First Affiliated Hospital， Army Medical University （Third Military Medical University）， Chongqing， China
出版时间: 2026-05-15 doi: 10.16016/j.2097-0927.202602079
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摘要
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目的

唾液酸化修饰作为一种重要的翻译后修饰，在细胞识别、信号转导等过程中发挥关键作用，通过探究α-2，3型唾液酸化修饰在成骨与成软骨分化过程中的作用，进一步明确其通过调控细胞外基质稳态对骨发育进程的影响，为骨骼发育障碍等疾病提供新的理论依据和潜在干预靶点。

方法

通过公共数据集GSE109503（成软骨分化）和GSE113253（成骨分化）分析唾液酸转移酶家族基因在成软骨与成骨分化中的表达谱，结合MC3T3-E1成骨细胞和ATDC5成软骨细胞模型进行体外分化实验进行qRT-PCR检测，筛选唾液酸转移酶家族核心差异基因（筛选阈值|Log₂FC|>1，P<0.05）。利用慢病毒构建稳定的α-2，3型唾液酸化修饰缺陷的MC3T3-E1成骨细胞和ATDC5成软骨细胞模型，分别进行成骨或成软骨诱导7、14 d，通过ALP染色、茜素红S染色、阿尔辛蓝染色观察分化能力，荧光定量PCR和Western blotting检测成骨标志基因（Col1a1、Sp7）和软骨标志基因（Col2a1）以及蛋白的表达。对α-2，3型唾液酸化修饰缺陷的MC3T3-E1细胞（成骨诱导7 d）和ATDC5细胞（成软骨诱导7 d）进行转录组测序，通过GO和KEGG富集分析解析差异基因的生物学功能。体内实验选取新生C57BL/6小鼠（雌雄各半，体质量1.0~1.5 g，出生当日），所有小鼠按随机数字表法分为（n=6）：唾液酸酶处理组［腹腔注射唾液酸酶（0.2 U/次，隔天1次，持续4周）］和对照组（注射等体积生理盐水）；采用Micro-CT分析股骨骨微结构参数。

结果

公共数据集显示仅St3gal1在成骨与成软骨分化中均显著上调（|Log₂FC|>1，P<0.05）；细胞体外分化模型验证了St3gal1在两种分化过程中均显著上调（P<0.000 1）。与公共数据集转录组测序结果相一致，证明了St3gal1介导的α-2，3型唾液酸化修饰伴随成骨与成软骨的分化进程。干扰α-2，3型唾液酸化修饰后，MC3T3-E1细胞ALP染色和茜素红S染色显著减弱，Col1a1和Sp7的mRNA表达分别降至对照组的60.7%（P<0.000 1）和49%（P<0.000 1）；蛋白水平同步降低，分别降至对照组的61.5%（P=0.000 2）和56.1%（P=0.000 3）；ATDC5细胞阿尔辛蓝染色显著减弱，Collagen Ⅱ蛋白表达降至对照组的43.1%（P<0.000 1）。转录组测序结果显示，差异基因在2组细胞中均显著定位于细胞外基质结构，分子功能均与细胞外基质结构组成相关；通路富集分析显示，差异基因均显著富集于ECM-受体互作等相关信号通路，提示唾液酸化修饰可能通过细胞外基质稳态等多条信号通路调控成骨与成软骨分化进而参与骨发育进程（|Log₂FC|>1，FDR<0.05）。体内实验证实，与对照组相比，唾液酸酶处理组小鼠股骨骨密度下降0.078 g/cm3（P<0.000 1）、骨小梁体积分数下降5.512%（P<0.000 1）、皮质骨厚度下降0.012 mm（P=0.001 1）及骨小梁数量下降1.39/mm（P<0.000 1）、骨小梁厚度下降0.002 3 mm（P=0.026 7）、骨小梁分离度增加0.35 mm（P<0.000 1），提示骨骼发育异常。

结论

α-2，3型唾液酸化修饰通过调控细胞外基质稳态正向调节成骨与成软骨分化，在骨骼发育中发挥关键作用。骨微环境中唾液酸化修饰可能成为骨骼发育不良性疾病的潜在干预靶点。

唾液酸化修饰  /  细胞外基质  /  骨骼发育  /  成骨分化  /  成软骨分化
Objective

Sialylation, an important post-translational modification, plays a key role in processes such as cell recognition and signal transduction. This study aims to explore the role of α-2,3 sialylation in osteogenic and chondrogenic differentiation, further elucidate its impact on bone development by regulating extracellular matrix (ECM) homeostasis, and provide novel theoretical basis and potential intervention targets for disorders of skeletal development.

Methods

The expression profiles of sialyltransferase family genes in osteogenic and chondrogenic differentiation were analyzed using public datasets GSE109503 (chondrogenic differentiation) and GSE113253 (osteogenic differentiation). In vitro differentiation experiments were conducted using MC3T3-E1 osteoblast and ATDC5 cells, and qRT-PCR was performed to screen for core differentially expressed genes (DEGs) in the sialyltransferase family (screening threshold |Log₂FC|>1, P<0.05). Stable α-2,3-type sialylation-deficient MC3T3-E1 and ATDC5 cells were constructed using lentiviral vectors, followed by osteogenic or chondrogenic induction for 7 and 14 d. Differentiation capacity was evaluated by ALP staining, Alizarin Red S staining, and Alcian blue staining. The expression of osteogenic marker genes (Col1a1, Sp7) and chondrogenic marker gene (Col2a1) was detected by qRT-PCR and Western blotting. Transcriptome sequencing was performed on α-2,3 sialylation-deficient MC3T3-E1 cells (osteogenic induction for 7 d) and ATDC5 cells (chondrogenic induction for 7 d), and biological functions of DEGs were analyzed with GO and KEGG enrichment analyses. For in vivo experiments, newborn C57BL/6 mice (half male and half female, body weight 1.0 to 1.5 g, on the day of birth) were randomly divided into 2 groups: an sialidase-treated group (intraperitoneally injected with sialidase, 0.2 U/dose, every other day for 4 weeks), and a control group (same volume of normal saline), with 6 animals in each group. Micro-CT scanning was conducted to analyze the bone microstructure parameters of the femur.

Results

Public dataset analysis revealed that only St3gal1 was significantly upregulated during both osteogenic and chondrogenic differentiation (|Log₂FC| >1, P<0.05). The in vitro cell differentiation model confirmed that St3gal1was significantly upregulated in both differentiation processes (P<0.000 1). Consistent with the public dataset transcriptome sequencing results, this demonstrated that St3gal1-mediated α-2,3-type sialylation accompanies the progression of osteogenic and chondrogenic differentiation. Following disruption of α-2,3 sialylation, ALP staining and Alizarin Red S staining in MC3T3-E1 cells were significantly attenuated, along with the mRNA expression levels of Col1a1and Sp7reduced to 60.7% (P<0.000 1) and 49% (P<0.000 1) of the control group, respectively, and corresponding protein levels decreasing to 61.5% (P=0.000 2) and 56.1% (P=0.000 3), respectively. In ATDC5 cells, Alcian Blue staining was markedly diminished, and CollagenⅡ protein expression was reduced to 43.1% of the control group (P<0.000 1). Transcriptomic sequencing results demonstrated that DEGs in both cell types were significantly enriched to ECM structure, and molecular functions were associated with ECM structural constituent. Pathway enrichment analyses revealed that DEGs were significantly enriched in ECM-receptor interaction and related signaling pathways (|Log₂FC|>1, FDR<0.05), suggesting that sialylation may regulate osteogenic and chondrogenic differentiation through multiple pathways, including ECM homeostasis, thereby contributing to bone development. In vivo experiments confirmed that, the sialidase-treated group exhibited reductions in femoral bone mineral density (decreased by 0.078 g/cm³, P<0.000 1), trabecular bone volume fraction (decreased by 5.512%, P<0.000 1), cortical thickness (decreased by 0.012 mm, P=0.001 1), trabecular number (decreased by 1.39/mm, P<0.000 1), and trabecular thickness (decreased by 0.002 3 mm, P=0.026 7), and an increase in trabecular separation (increased by 0.35 mm, P<0.000 1) when compared with the control group, indicating impaired skeletal development.

Conclusion

α-2,3 Sialylation positively regulates osteogenic and chondrogenic differentiation through modulating ECM homeostasis and plays an essential role in skeletal development. Sialylation within the bone microenvironment may serve as a potential intervention target for skeletal dysplasia disorders.

sialylation modification  /  extracellular matrix  /  skeletal development  /  osteogenic differentiation  /  chondrogenic differentiation
张东阳, 汤勇, 谭玖琳, 代其杰, 许建中, 窦策. α-2，3型唾液酸化修饰通过调控细胞外基质稳态促进成骨与成软骨分化参与骨骼发育. 陆军军医大学学报, 2026 , 48 (9) : 1167 -1180 . DOI: 10.16016/j.2097-0927.202602079
Dongyang ZHANG, Yong TANG, Jiulin TAN, Qijie DAI, Jianzhong XU, Ce DOU. Alpha-2,3 sialylation promotes osteogenic and chondrogenic differentiation by regulating extracellular matrix homeostasis to participate in skeletal development[J]. Journal of Army Medical University, 2026 , 48 (9) : 1167 -1180 . DOI: 10.16016/j.2097-0927.202602079
正文
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骨骼发育是一个复杂且精密的生物学过程，涉及复杂的基因网络、表观遗传调控和细胞微环境的精细协作［1］。在这一过程中，作为骨骼生长模板的软骨组织，以及承担支撑功能的矿化骨组织，其构建都高度依赖于细胞外基质的合成与组装［2-3］。软骨细胞和成骨细胞是2个关键的参与者，核心任务之一是大量合成并分泌特定的细胞外基质成分，紧密协同共同构建和维护骨骼系统［4］。软骨细胞负责形成软骨雏形，这是软骨内成骨过程中骨骼生长的初始框架［5］。而成骨细胞则是负责沉积骨基质、促进骨矿化的特化细胞，最终参与骨的形成与重塑。这些由细胞分泌的基质分子不仅构成了组织特有的三维支架，为后续的细胞黏附、迁移和增殖提供物理支持；它们还能够结合并递送多种生长因子，并通过整合素等受体将信号传导至细胞内，从而精密调控细胞的分化、存活与功能。因此，深入理解软骨细胞和成骨细胞分化过程中合成与重塑细胞外基质过程中的分子机制，不仅对阐明正常骨骼发育至关重要，也对治疗多种骨相关疾病，如骨质疏松症、骨关节炎和骨骼发育不良等，具有重要的临床意义。
唾液酸化是一种重要的翻译后修饰过程，该过程由唾液酸转移酶特异性催化完成。这些酶将活化的唾液酸供体转移到糖链末端（如半乳糖或N-乙酰半乳糖胺等）上。唾液酸是一类带负电荷的九碳单糖（最常见的是N-乙酰神经氨酸），通常位于糖链的最外端。唾液酸携带强负电荷，能增加分子的亲水性和空间位阻，从而影响蛋白质的构象、稳定性和相互作用［6］，在细胞识别、信号转导、免疫调节及感染等生理过程中发挥关键作用［7-8］。随着研究的深入，唾液酸化修饰在多种疾病发生发展中的作用逐渐被揭示，包括肿瘤转移［9］、神经退行性疾病［10］和自身免疫病［11］等。然而，唾液酸化修饰在骨骼发育过程中的调控机制研究仍处于起步阶段，目前的研究提示唾液酸化修饰与破骨细胞的分化、代谢和功能密切相关［12-13］，鲜有研究从细胞外基质稳态这一动态平衡视角，系统解析唾液酸化修饰在骨骼发育中的生物学功能。事实上，基质稳态的维持不仅依赖于成骨细胞与软骨细胞的合成活性，更与其介导的信号传导和细胞间通讯精密耦合。因此，深入探索唾液酸化修饰如何通过影响骨微环境中细胞外基质稳态，从而协调软骨与成骨细胞功能，对于揭示骨骼发育的分子机制具有重要科学价值。
为探究唾液酸化修饰对细胞外基质功能的影响，本研究选取了α-2，3型唾液酸化修饰作为干预靶点。ST3β-半乳糖苷α-2， 3唾液酸转移酶1是一种Ⅱ型膜蛋白，定位于高尔基体，催化唾液酸以α-2，3键连接到含半乳糖的糖蛋白或糖脂底物上，在O-聚糖修饰、神经节苷脂合成及免疫细胞稳态［14］中发挥重要作用。需指出的是，唾液酸转移酶家族包含20个成员，部分酶之间存在底物重叠与功能冗余［15］。公共数据集及预实验显示，St3gal1在成骨与成软骨分化过程中表达显著上调，提示其可能介导分化相关的唾液酸化修饰。本研究通过干预St3gal1的表达构建了α-2，3型唾液酸化修饰缺陷的细胞模型，并利用转录组学技术系统解析唾液酸化修饰缺陷后的基因网络变化，重点关注细胞外基质相关通路及基质-细胞信号传导的改变，以期为揭示唾液酸化修饰在骨骼发育中的调控机制提供新的理论基础和实验依据。
1　材料与方法
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1.1　实验动物和细胞
实验所需12周C57BL/6孕鼠购自陆军军医大学实验动物中心［生产许可证：SCXK（渝）2022-0010］。所有动物于温度（24±1）℃、相对湿度50%±5%、12 h/12 h明暗循环条件下饲养。小鼠成软骨细胞系ATDC5和小鼠成骨前体细胞系MC3T3-E1购自武汉普诺赛生命科技有限公司。ATDC5细胞来源于小鼠胚胎畸胎瘤，是具有软骨祖细胞特性的永生化细胞系，在软骨诱导培养基刺激下可向软骨细胞分化，形成软骨小结，表达Ⅱ型胶原和X型胶原，是研究软骨发生过程的经典体外模型。MC3T3-E1细胞来源于C57BL/6小鼠胚胎颅顶，是成骨前体细胞的永生化细胞系，可在抗坏血酸和β-甘油磷酸钠诱导下向成骨细胞分化，沉积矿化基质，表达成骨标志基因，是研究成骨分化的经典体外模型。
1.2　动物模型构建
母鼠分娩成功后，将其新生乳鼠用于实验。随机选取24只新生乳鼠，雌雄各12只，体质量1.0~1.5 g，出生当日（记为P0）。所有小鼠按随机数字表法分为（n=6）：唾液酸酶处理组［腹腔注射唾液酸酶（0.2 U/次，隔天1次，持续4周）］和对照组（注射等体积生理盐水）。实验采用同窝对照设计，即将同一窝内的乳鼠随机分配至不同处理组，以最大限度地控制遗传背景和出生环境差异带来的影响。模型构建始于乳鼠出生当日（记为P0）。唾液酸酶处理组乳鼠经腹腔注射唾液酸酶（Sialidase；Merck，德国；来源于产气荚膜梭菌，色谱纯化，比活性50~150 U/mg蛋白），注射剂量为每次0.2 U（溶于无菌生理盐水，总体积100 μL），注射频率为隔天1次，该干预措施持续进行4周。唾液酸酶制剂以无菌生理盐水配制的溶液形式提供，使用前用无菌生理盐水稀释至所需浓度，分装后于-20 ℃保存，避免反复冻融。对照组乳鼠则在相同时间点注射等体积的生理盐水。
本研究所涉及的所有动物操作程序严格遵守动物福利伦理规范，并已获得陆军军医大学实验动物福利伦理委员会审批（AMUWEC20242104）。所有动物在标准化环境［温度（22±1）℃，湿度55%±5%，12 h明/暗循环］中适应性饲养1周，可自由获取灭菌水和标准饲料。严格遵守动物福利伦理原则，任何出现无法进食或饮水、体质量较基准值下降超过20%或出现严重痛苦迹象（如持续抽搐、严重震颤或瘫痪）的小鼠，在实验预定终点前在深度麻醉状态下实施安乐死。
1.3　Micro-CT 扫描和分析小鼠股骨组织
4周龄小鼠用2%戊巴比妥钠麻醉处死后，于膝关节处离断股骨和胫骨后，向近端分离至髋关节并进行离断，获得小鼠股骨样本，置于4%多聚甲醛组织固定液中进行固定，固定至少24 h后上机扫描。股骨样本采用Bruker MicroCT Skyscan 1272系统（Kontich，Belgium）进行扫描成像，扫描分辨率为7 μm体素。获取的原始数据通过NRECON软件（Kontich，Belgium）进行三维重建以便详细观察。使用DataViewer软件（版本1.5.6.2，Bruker，Kontich，Belgium）在重建图像上精确界定感兴趣区域，即股骨生长板区域（自股骨远端向近端延伸2 mm范围）。进一步采用CTAN软件（版本1.20.8.0，Bruker，Kontich，Belgium）进行定量分析，获取骨体积分数及相关区域参数。
1.4　MC3T3-E1细胞培养及成骨诱导
MC3T3-E1细胞使用含10%胎牛血清及1%青霉素/链霉素的α-MEM培养基（Gibco，中国）进行常规培养。将细胞以约60%的汇合度接种后，更换为成骨诱导培养基进行培养。诱导培养基使用小鼠MC3T3-E1细胞成骨诱导分化试剂盒（OriCell，中国）。成骨诱导期间，每3天更换1次新鲜诱导培养基。所有细胞在37 ℃、5%CO₂的恒温湿润培养箱中培养。
1.5　ATDC5细胞培养及诱导分化
ATDC5细胞使用含5%胎牛血清及1%青霉素/链霉素的DMEM/F-12（1∶1；1X）培养基（SPERIKON，中国）进行常规培养。细胞密度调整至1×10⁵/mL后用于后续诱导分化实验。软骨诱导分化培养基使用OriCell®小鼠骨髓间充质干细胞成软骨诱导分化试剂盒（OriCell，中国）。软骨诱导期间，每2天更换1次软骨诱导培养基。所有细胞在37 ℃、5%CO₂的恒温湿润培养箱中培养。
1.6　慢病毒包装
靶向St3gal1基因的shRNA慢病毒载体及其阴性对照载体由广州派真生物技术有限公司设计与构建。将携带sh-St3gal1序列的慢病毒载体（LV-U6-Neo）或阴性对照载体，与慢病毒包装质粒系统（pMD2.G和psPAX2）以适当比例共转染至对数生长期的HEK293T细胞中（Procell，中国）。转染采用聚乙烯亚胺（PEI）方法进行。转染后48、72 h，分别收集含有慢病毒颗粒的细胞培养上清液，经0.45 μm滤膜过滤后，使用超速离心法进行浓缩和纯化，分装后于-80 ℃保存备用。
1.7　细胞感染与稳转株筛选
分别将ATDC5和MC3T3-E1以适宜密度接种于培养板中。待细胞生长至约50%汇合度时，更换为含有sh-St3gal1的慢病毒颗粒（LV-sh-St3gal1）及阴性对照慢病毒颗粒（LV-NC）的完全培养基进行感染。感染12 h后，更换为新鲜的完全培养基继续培养。感染72 h后，向培养基中加入适宜浓度的嘌呤霉素进行持续筛选。该实验分为：稳定敲低St3gal1基因细胞系（LV-sh-St3gal1）组、阴性对照的细胞系（LV-NC）组以及非处理（Control）组。通过荧光定量PCR验证St3gal1在mRNA上的敲低效率。LV-sh-St3gal1：正义（5'→3'）CCGGCTGGCAATGTGGATCCTATCTCGAGATAGGATCCACATTGCCAGTTTTTG；反义（5'→3'）AATTCAAA-AACTGGCAATGTGGATCCTATCTCGAGATAGGATCC-AACATTGCCAG。LV-NC：正义（5'→3'）CCGGCAAC-AAGATGAAGAGCACCAACTCGAGTTGGTGCTCTTCA-TCTTGTTGTTTTTG；反义（5'→3'）AATTCAAAAACA-ACAAGATGAAGAGCACCAACTCGAGTTGGTGCTCTT-CATCTTGTTG。
1.8　茜素红S染色检测矿化结节的形成
Control、LV-NC、LV-sh-St3gal1组MC3T3-E1细胞经过成骨诱导培养基培养14 d后，使用4%多聚甲醛（赛维尔生物，中国）固定细胞，随后加入茜素红S染色液（OriCell，中国），于37 ℃孵育染色。染色完成后，使用光学显微镜直接观察并拍照记录显色结果。
1.9　ALP染色检测碱性磷酸酶活性
使用BCIP/NBT碱性磷酸酶显色试剂盒（碧云天，中国）进行碱性磷酸酶染色。具体方法如下：Control、LV-NC、LV-sh-St3gal1组MC3T3-E1细胞经过成骨诱导培养基培养7 d后，使用4%多聚甲醛固定细胞，随后加入BCIP/NBT染色工作液，于37 ℃避光孵育30 min。孵育结束后，用PBS洗涤3次，使用光学显微镜直接观察并拍照记录显色结果。
1.10　阿尔辛蓝染色检测软骨基质的形成
使用阿尔辛蓝染色液（OriCell，中国）进行阿尔辛蓝染色。具体方法如下：Control、LV-NC、LV-sh-St3gal1组ATDC5细胞接种于12孔板中，密度调整为1×10⁵/mL，随后使用软骨诱导培养基进行诱导分化培养7 d。诱导结束后，使用4%多聚甲醛于37 ℃固定细胞30 min，随后加入阿尔辛蓝染色液。使用光学显微镜直接观察并拍照记录显色结果。
1.11　荧光定量PCR检测细胞中基因表达情况
使用RNA快速纯化试剂盒（ES science，中国）提取细胞总RNA。使用PrimeScript™ RT reagent Kit with gDNA Eraser（Perfect Real Time，TaKaRa）将提取的RNA反转录为cDNA。使用TB Green® Premix Ex Taq™Ⅱ（Tli RNaseH Plus，TaKaRa）配置PCR反应体系，并置于CFX96 Touch实时荧光定量PCR检测系统（Bio-Rad）上进行qPCR反应。目的基因及内参基因GAPDH的特异性引物如表1所示。
1.12　Western blotting检测细胞中蛋白表达情况
使用RIPA裂解液（碧云天，中国）裂解细胞。采用BCA蛋白浓度测定试剂盒（碧云天，中国）测定蛋白浓度。取50 μg蛋白样品与上样缓冲液（碧云天，中国）混合，经SDS-PAGE电泳分离后，转移至PVDF膜（Sigma Aldrich，德国）。转移完成后，用5%脱脂牛奶封闭PVDF膜以阻断非特异性结合。封闭1 h后，将膜与以下一抗于4 ℃孵育过夜：GAPDH（1∶1 000；赛维尔生物，中国）、Osterix（1∶1 000；Abclonal，中国）、Col1a1（1∶5 000；ABclonal，中国）、Col2a1（1∶1 000；ABclonal，中国）。使用TBST清洗膜4次后，加入辣根过氧化物酶（HRP）标记的二抗（1∶1 000；碧云天，中国），于37 ℃孵育80 min。使用ECL Plus化学发光底物显色，并在凝胶成像系统中采集图像。
1.13　NCBI GEO数据集筛选分析
为探究唾液酸转移酶家族在间充质干细胞成骨与成软骨分化过程中的表达特征，在GEO数据库中，以“mesenchymal stem cell”“osteogenic differentiation”和“chondrogenic differentiation”为关键词进行检索，筛选获得了成软骨诱导相关数据集GSE109503及成骨诱导相关数据集GSE113253。利用GEO内置的GEO2R在线分析工具分别对2个数据集进行处理，识别并提取在成软骨和成骨诱导过程中显著差异表达的基因。通过GeneCards数据库（https://www.genecards.org/）获取唾液酸转移酶家族的基因列表。为进一步筛选与该分化过程密切相关的家族成员，将上述2组差异基因分别与唾液酸转移酶基因列表进行Venn分析，最终获得在成骨和成软骨分化中共同或特异性涉及的唾液酸转移酶家族核心差异基因。
1.14　转录组测序及分析
收集LV-NC组与LV-sh-St3gal1组的MC3T3-E1细胞（成骨诱导7 d）和ATDC5细胞（成软骨诱导7 d）样本，每组设置3个生物学重复。使用TRIzol试剂提取细胞总RNA，通过Agilent 2100 Bioanalyzer检测RNA完整性（RIN>7.0）及纯度。使用NEBNext® Ultra™ RNA Library Prep Kit for Illumina构建转录组测序文库，具体流程包括：利用Oligo（dT）磁珠富集mRNA、片段化缓冲液将mRNA打断为短片段、以随机引物合成第一链cDNA和第二链cDNA、末端修复、加A尾并连接测序接头、片段筛选及PCR扩增。
文库质检合格后，于Illumina NovaSeq 6000平台进行双端150 bp高通量测序。测序原始数据（Raw Reads）经FastQC软件进行质量控制后，使用Trim Galore去除接头序列及低质量碱基（Q<20），获得高质量序列（Clean Reads）。采用HISAT2软件将Clean Reads比对至小鼠参考基因组（GRCm39/mm39），利用FeatureCount软件进行基因表达定量。差异表达分析使用DESeq2 R包，筛选阈值为|Log₂FC|>1、FDR<0.05。基于差异基因列表，使用ClusterProfiler R包进行GO功能富集分析及KEGG通路富集分析，显著性阈值设定为FDR<0.05。
1.15　统计学分析
使用GraphPad Prism 7.0软件对数据进行统计分析。具有正态分布的计量资料以x¯±s表示，两组之间比较采用独立t检验，三组样本的统计比较采用单因素方差分析，以P<0.05为差异具有统计学意义。
2　结果
收起
2.1　唾液酸转移酶家族基因在成骨和成软骨分化过程中差异性表达
为了初步探究唾液酸转移酶介导的唾液酸化修饰对成骨和成软骨分化的影响，对2个数据集的转录组数据进行分析，唾液酸转移酶家族部分基因同时参与两种分化进程（图1A~C）。图中标注了ST3GAL1、ST3GAL2、ST3GAL4和ST6GAL1的位置。转录组数据结果显示，唾液酸转移酶家族仅有ST3GAL1在成骨、成软骨两种分化进程中表达均上调；ST3GAL2随分化进程表达均无明显差异；ST3GAL4表达在成骨分化进程中无明显差异，在成软骨分化进程中上调；ST6GAL1表达在成骨分化进程中无明显差异，在成软骨分化进程中下调（图1A）。为了进一步在体外实验进行验证，在成骨细胞系MC3T3-E1和成软骨细胞系ATDC5分别诱导分化0、7、14 d后，通过荧光定量PCR检测了唾液酸转移酶家族中差异表达基因St3gal1、St3gal2、St3gal4与St6gal1的表达变化。与公共数据集转录组测序相符的是，St3gal1的表达在两种细胞系分化过程中均显著上调（图1D、E）。上述结果显示，St3gal1在成骨细胞与成软骨细胞分化过程中，其表达水平均随分化进程逐渐增强，提示α-2，3型唾液酸化修饰可能在此类细胞分化调控中扮演重要角色。
2.2　α-2，3型唾液酸化修饰缺陷显著阻滞成骨细胞的矿化沉积与早期成骨表型
为了进一步确定α-2，3型唾液酸化修饰对MC3T3-E1细胞成骨分化能力的影响，构建α-2，3型唾液酸化修饰缺陷的细胞模型。免疫荧光染色证实，LV-sh-St3gal1组α-2，3型唾液酸化修饰细胞比例下降。与LV-NC组相比，LV-sh-St3gal1组细胞St3gal1的mRNA水平显著降低（P=0.000 1，图2A）。这表明细胞模型构建成功。在此基础上，评估了α-2，3型唾液酸化修饰缺陷对成骨分化的影响。ALP染色结果显示，成骨诱导7 d后，LV-sh-St3gal1组的蓝紫色染色深度与范围均明显弱于LV-NC组（P<0.000 1，图2B），提示其早期成骨分化活性受损。进一步通过茜素红S染色评估终末期矿化过程发现，成骨诱导14 d后，与LV-NC组相比，LV-sh-St3gal1组形成的红色矿化结节在数量、大小及染色深度上均显著减少（P<0.000 1，图2C）。综上所述，α-2，3型唾液酸化修饰缺陷不仅抑制了MC3T3-E1细胞的早期成骨分化活性，也显著削弱了其终末矿化能力。
2.3　转录组学揭示了α-2，3型唾液酸化修饰缺陷通过影响成骨微环境中细胞外基质稳态来下调成骨分化信号通路
根据对LV-sh-St3gal1干预组与对照组的比较分析，差异表达基因热图与火山图展示了对照组（LV-NC）与St3gal1敲低组（LV-sh-St3gal1）之间显著差异表达基因的表达聚类情况（|Log₂FC|>1，FDR<0.05，图3A、B）。气泡图展示显著富集的与骨骼发育相关的生物过程（BP）、细胞成分（CC）和分子功能（MF）。差异表达基因在细胞外基质组装、骨化及间充质/软骨/成骨细胞分化等生物学过程中显著富集（图3C），并主要定位在细胞外基质结构与转录调控复合体等细胞成分中（图3D），其分子功能涉及激酶活性、细胞外基质结构组成及转录因子活性调控等（图3E）；KEGG通路分析进一步表明这些基因富集于Wnt、PI3K-Akt、MAPK及ECM-受体相互作用等多条信号通路（图3F），提示α-2，3型唾液酸化修饰可能通过调控细胞外基质稳态与多信号网络参与骨骼发育与成骨细胞分化过程。
2.4　α-2，3型唾液酸化修饰缺陷破坏了成骨关键基质蛋白合成及成骨转录因子的表达
为了进一步明确α-2，3型唾液酸化修饰对MC3T3-E1细胞成骨分化的影响，通过转录组测序检测出与成骨相关的差异基因（图4A），并进一步通过荧光定量PCR对部分基因进行验证。结果显示，在LV-sh-St3gal1组细胞中，成骨分化关键基因Col1a1和Sp7的mRNA表达水平均较LV-NC组显著下调（P<0.001，图4B）。此外，Western blotting结果也进一步证实，这些基因在蛋白水平的表达也呈现同步的显著降低（P=0.000 3，P=0.000 2，图4C）。上述结果进一步明确了α-2，3型唾液酸化修饰通过调控细胞外基质关键蛋白影响成骨分化进程的重要作用。
2.5　干扰α-2，3型唾液酸化修饰破坏软骨细胞的基质合成与软骨结节形成能力
为了明确干扰α-2，3型唾液酸化修饰对ATDC5细胞成软骨分化的影响，构建了稳定干扰α-2，3型唾液酸化修饰的细胞模型。免疫荧光染色证实，LV-sh-St3gal1组α-2，3型唾液酸化修饰细胞比例下降。与LV-NC相比，LV-sh-St3gal1细胞中St3gal1的mRNA表达水平显著降低（P=0.000 2，图5A），表明细胞模型构建成功。成软骨诱导7 d后进行阿尔辛蓝染色。LV-NC组形成了多个边界清晰、染色深蓝的典型软骨结节。相比之下，LV-sh-St3gal1组的蓝色染色显著减弱，形成的结节数量更少、体积更小且染色较浅（图5B）。此外，Western blotting结果也进一步证实，在蛋白层面，与LV-NC组相比，LV-sh-St3gal1组软骨分化的标志物也呈现同步的显著降低（P=0.000 3，图5C）。提示干扰α-2，3型唾液酸化修饰抑制了ATDC5细胞的基质合成与软骨结节形成能力。
2.6　转录组学揭示了α-2，3型唾液酸化修饰缺陷通过影响软骨微环境中细胞外基质稳态来下调软骨分化信号通路
为探究α-2，3型唾液酸化修饰对成软骨分化的转录调控作用，对LV-Sh-St3gal1组与LV-NC组ATDC5细胞成软骨诱导后进行转录组测序。热图显示2组样本表达谱明显分离，α-2，3型唾液酸化修饰缺陷显著改变了成软骨分化相关基因的表达特征（图6A）。火山图展示了差异表达基因的整体分布，下调基因数量多于上调基因（图6B），提示α-2，3型唾液酸化修饰在维持成软骨分化相关基因表达中主要起正向调控作用。GO富集分析表明，差异基因显著富集于软骨内成骨、软骨发育、骨骼系统形态发生等骨发育核心生物学过程；细胞成分分析显示，差异基因定位于含胶原的细胞外基质、基底膜、钙通道复合物及高尔基体腔等结构，此外在极性生长位点与生长锥中也高度富集；分子功能分析显示，差异基因显著富集于蛋白酶结合以及细胞外基质结构组成等功能。上述结果提示，差异基因可能通过调控细胞外基质重塑在骨骼发育与成软骨分化过程中发挥关键作用。KEGG通路则以ECM-受体相互作用等发育相关通路最为显著（图6C、D）。上述结果表明，α-2，3型唾液酸化修饰缺陷可能通过细胞外基质ECM-受体密切相关的通路来干预成软骨细胞分化进程。
2.7　唾液酸酶抑制小鼠的骨形成与发育
为了直接评估唾液酸化修饰在骨形成与发育中的作用，对新生小鼠腹腔注射唾液酸酶。唾液酸酶通过移除细胞表面或生物分子末端的唾液酸残基，从而破坏唾液酸化修饰。处理4周后，采用Micro-CT对小鼠股骨的生长板及骨组织进行了分析（图7）。与同窝对照小鼠相比，唾液酸酶处理组小鼠的股骨骨密度（P<0.000 1）、骨小梁体积分数（P<0.000 1）、皮质骨厚度（P=0.001 1）、骨小梁数量（P<0.000 1）及骨小梁厚度（P=0.026 7）均显著降低，而骨小梁分离度则相应增加（P<0.000 1）。这些结果共同强调了唾液酸化修饰对正常骨骼发育和形态发生是不可或缺的。
3　讨论
收起
3.1　唾液酸化修饰正向调控成骨与成软骨分化进程
本研究系统证实α-2，3型唾液酸化修饰在成骨与成软骨分化进程中均呈显著上调，其缺陷同时损害MC3T3-E1细胞与ATDC5细胞的分化能力，提示α-2，3型唾液酸化修饰可能发生在成骨-软骨谱系分化的上游共同节点。既往研究将唾液酸化修饰的功能主要局限于肿瘤细胞迁移、免疫逃逸及化疗抵抗［16-17］，本研究将其拓展至骨骼发育领域，并发现其在不同谱系细胞中介导相似的促分化效应，而下游效应基因却呈现谱系特异性。在成骨细胞中，α-2，3型唾液酸化修饰缺陷主要导致矿化结节形成减少、ALP活性降低，并下调成骨标志基因Col1a1和Sp7的表达；而在软骨细胞中，则表现为软骨结节形成受阻、阿尔辛蓝染色减弱以及Col2a1蛋白表达下降。这种同因异果的调控模式暗示，唾液酸化修饰并非直接调控成骨或软骨特异性基因，而更可能是通过对骨微环境中共享信号通路受体或细胞外基质蛋白的唾液酸化修饰，间接为谱系特异性转录程序的启动提供适宜的微环境。转录组数据进一步显示，2组细胞中差异基因虽均富集于ECM-受体相互作用等共同通路，但具体富集的基因集存在差异，这可能是导致谱系特异性表型的重要原因。体内唾液酸酶干预实验进一步证实，整体抑制唾液酸化修饰可导致新生小鼠股骨骨密度、骨小梁体积分数、皮质骨厚度、骨小梁数量及骨小梁厚度显著降低，从整体水平确证了唾液酸化修饰在骨骼形态发生中的必要性。综上，通过唾液酸酶处理整体削减唾液酸化修饰水平会明显损害小鼠骨骼的整体发育，而体外干扰唾液酸化修饰则会抑制成骨与成软骨分化过程，提示唾液酸化修饰是发育过程中成骨与成软骨细胞正常分化所必要的翻译后修饰。
3.2　唾液酸化修饰可能通过调控细胞外基质稳态与多条信号通路来影响骨骼发育
为明确唾液酸化修饰调控成骨与成软骨分化的分子基础，本研究对干扰唾液酸化修饰的成骨与成软骨细胞进行了转录组测序。测序结果清晰提示，干扰唾液酸化修饰所导致的差异表达基因在2组细胞中均显著富集于细胞外基质组织、软骨内成骨、骨骼系统形态发生及骨化等骨发育核心生物学进程。这一跨细胞系的一致性富集特征表明，唾液酸化修饰可能通过共同的下游通路参与骨骼发育全局性调控。
进一步分析显示，差异基因显著富集于ECM-受体相互作用、Wnt、PI3K-Akt及Notch等多条骨发育关键信号通路。细胞外基质是唾液酸化修饰的重要平台，胶原、纤连蛋白及蛋白聚糖等核心基质成分的唾液酸化修饰状态直接影响其构象稳定性、整合素亲和力及下游信号转导能力。已有研究证实，纤连蛋白的唾液酸化可调控成骨细胞整合素信号［18-19］，而糖胺聚糖的硫酸化与唾液酸化则协同维持软骨基质稳态［20-21］。本研究结果提示，唾液酸化修饰缺陷可能导致多种基质蛋白糖基化谱改变，破坏ECM-细胞间信号对话，进而从微环境层面影响骨发育进程。
此外，氧化应激通路在2组细胞中均显著富集，唾液酸化修饰缺陷可能暴露免疫原性或氧化敏感表位［22］，诱发内质网应激与线粒体功能障碍［23-24］，这为解释唾液酸化修饰缺陷所致分化阻滞提供了代谢层面的潜在机制。综上，转录组测序从全基因组水平揭示了唾液酸化修饰缺陷对骨发育进程的系统性扰动，提示可能通过对细胞外基质及膜受体糖蛋白的末端唾液酸化修饰，整合多条骨发育相关信号网络，协同调控成骨与成软骨分化。
本研究尚存若干不足：①唾液酸化修饰作用的直接糖蛋白底物尚未鉴定。唾液酸转移酶不直接结合DNA，其调控基因表达的能力必然通过改变膜受体或分泌因子的糖基化状态实现。后续需联合凝集素富集、糖蛋白组学及邻近标记技术，系统绘制成骨与成软骨细胞中唾液酸化谱，并筛选核心效应分子。②关于唾液酸酶腹腔注射影响骨骼发育的途径，结合相关文献，可能通过以下途径实现：a.循环系统介导的直接作用是重要基础，GELBERG等［25］证实腹腔注射的唾液酸酶可被吸收进入血液循环并作用于肾小球，CHOI等［26］进一步证明该酶能通过腹膜毛细血管网进入体循环，随血流分布至全身组织，骨骼作为高度血管化器官可直接受到循环中酶的作用；b.免疫细胞介导的间接调控可能协同参与，KNOP等［27］发现腹腔注射唾液酸酶可显著增强巨噬细胞吞噬功能，活化的免疫细胞可迁移至骨骼微环境，通过释放细胞因子影响骨细胞功能；c.血清糖蛋白唾液酸化修饰状态改变引发的内分泌调节亦不可忽视，唾液酸酶处理后，血清中多种糖蛋白的稳定性可能因唾液酸化修饰状态改变而受到影响［28］，进而间接调控骨骼代谢。尽管如此，本研究尚未直接追踪唾液酸酶在体内的分布与代谢，后续需结合示踪技术解析其生物学途径。体内唾液酸酶注射为非特异性干预，无法区分不同细胞类型的各自贡献。本团队已构建St3gal1flox/flox小鼠，正与Prx1-Cre、Col2a1-Cre及Ocn-Cre品系交配，拟分别实现间充质谱系、软骨细胞及成熟成骨细胞中St3gal1的条件性敲除，以精准解析其在骨骼发育不同阶段、不同细胞中的自主性功能。③本研究主要聚焦于St3gal1，但公共数据显示St3gal2、St6gal1等其他家族成员在分化过程中也有差异表达。如MOHAMED等［15］研究所述，唾液酸转移酶家族成员间存在底物重叠与功能冗余。因此，这些基因是否在St3gal1敲低后发生代偿性上调，以及它们对成骨、成软骨分化的独立或协同贡献，尚需进一步研究。后续可采用多基因联合干预或条件性敲除动物模型，系统解析唾液酸转移酶家族在骨骼发育中的功能网络。
综上所述，本研究系统阐明了唾液酸化修饰通过调控成骨与成软骨分化中细胞外基质稳态参与骨与软骨发育进程。结果不仅加深了对糖基化修饰在骨骼生物学中功能的理解，也为进一步探究骨骼发育异常性疾病的分子机制提供了新的视角和潜在干预靶点。

文献
收起
参考文献 引证文献
排序方式：
1
STEGEN S， CARMELIET G. Metabolic regulation of skeletal cell fate and function［J］. Nat Rev Endocrinol， 2024， 20（7）： 399-413.
2
YUAN G X， LIN X X， LIU Y， et al. Skeletal stem cells in bone development， homeostasis， and disease［J］. Protein Cell， 2024， 15（8）： 559-574.
3
TROMPET D， MELIS S， CHAGIN A S， et al. Skeletal stem and progenitor cells in bone development and repair［J］. J Bone Miner Res， 2024， 39（6）： 633-654.
4
OLSEN B R， REGINATO A M， WANG W F. Bone development［J］. Annu Rev Cell Dev Biol， 2000， 16： 191-220.
5
DARBELLAY F， RAMISCH A， LOPEZ-DELISLE L， et al. Pre-hypertrophic chondrogenic enhancer landscape of limb and axial skeleton development［J］. Nat Commun， 2024， 15（1）： 4820.
6
BINDEMAN W E， FINGLETON B. Glycosylation as a regulator of site-specific metastasis［J］. Cancer Metastasis Rev， 2022， 41（1）： 107-129.
7
张嘉宁， 汪淑晶. 唾液酸生物学与人类健康和疾病［J］. 生命科学， 2011， 23（7）： 678-684.
ZHANG J N， WANG S J. Sialobiology in human health and disease［J］. Chin Bull Life Sci， 2011， 23（7）： 678-684.
8
SHIVATARE S S， SHIVATARE V S， WONG C H. Glycoconjugates： synthesis， functional studies， and therapeutic developments［J］. Chem Rev， 2022， 122（20）： 15603-15671.
9
许青， 段嘉蓉， 郑天清. 靶向唾液酸-Siglec在肿瘤免疫治疗中的研究进展［J］. 中国肿瘤临床， 2025， 52（2）： 81-85.
XU Q， DUAN J R， ZHENG T Q. Research progress on tumor immunotherapy targeting sialic acid-Siglec complexes［J］. Chin J Clin Oncol， 2025， 52（2）： 81-85.
10
CHENG S L， XIAO B， LUO Z H. Glycosylation in neuroinflammation： mechanisms， implications， and therapeutic strategies for neurodegenerative diseases［J］. Transl Neurodegener， 2025， 14（1）： 47.
11
SNEED S L， STRANDBERG E A， LAUREANO A F S， et al. Molecular determinants of sialylated IgG anti-inflammatory activity［J］. Proc Natl Acad Sci U S A， 2025， 122（20）： e2411600122.
12
YANG S F， HE Z Y， WU T， et al. Glycobiology in osteoclast differentiation and function［J］. Bone Res， 2023， 11（1）： 55.
13
DOU C， ZHEN G H， DAN Y， et al. Sialylation of TLR2 initiates osteoclast fusion［J］. Bone Res， 2022， 10（1）： 24.
14
PRIATEL J J， CHUI D， HIRAOKA N， et al. The ST3Gal-I sialyltransferase controls CD8+ T lymphocyte homeostasis by modulating O-glycan biosynthesis［J］. Immunity， 2000， 12（3）： 273-283.
15
MOHAMED K A， KRUF S， BÜLL C. Putting a cap on the glycome： Dissecting human sialyltransferase functions［J］. Carbohydr Res， 2024， 544： 109242.
16
LIN W D， FAN T C， HUNG J T， et al. Sialylation of CD55 by ST3GAL1 facilitates immune evasion in cancer［J］. Cancer Immunol Res， 2021， 9（1）： 113-122.
17
赵自豪， 郑文静， 张玲玲， 等. 唾液酸转移酶ST3GAL1促进胶质瘤恶性进展［J］. 细胞与分子免疫学杂志， 2025， 41（4）： 308-317.
ZHAO Z H， ZHENG W J， ZHANG L L， et al. Sialyltransferase ST3GAL1 promotes malignant progression in glioma［J］. Chin J Cell Mol Immunol， 2025， 41（4）： 308-317.
18
SINGH P， CARRAHER C， SCHWARZBAUER J E. Assembly of fibronectin extracellular matrix［J］. Annu Rev Cell Dev Biol， 2010， 26： 397-419.
19
PAN D， SONG Y H. Role of altered sialylation of the I-like domain of beta1 integrin in the binding of fibronectin to beta1 integrin： thermodynamics and conformational analyses［J］. Biophys J， 2010， 99（1）： 208-217.
20
郑雯， 蔡明详， 彭荟桢， 等. 不同硫酸化程度的糖胺聚糖成软骨作用的体外研究［J］. 华西口腔医学杂志， 2023， 41（4）： 395-404.
ZHENG W， CAI M X， PENG H Z， et al. Effect of glycosaminoglycans with different degrees of sulfation on chondrogenesis［J］. West China J Stomatol， 2023， 41（4）： 395-404.
21
BALI J P， COUSSE H， NEUZIL E. Biochemical basis of the pharmacologic action of chondroitin sulfates on the osteoarticular system［J］. Semin Arthritis Rheum， 2001， 31（1）： 58-68.
22
WU Y， MA W J， JIANG Y Y， et al. Chemoenzymatic synthesis of glycopeptide library Decodes Sialylation-dependent immunodominance to enable a potent multicomponent antitumor vaccine［J］. Angew Chem Int Ed， 2026， 65（9）： e25026.
23
FUCHS A L， SINGH B， JETMORE J W， et al. Mitochondrial dysfunction enhances influenza pathogenesis by up-regulating de novo sialic acid biosynthesis［J］. Sci Adv， 2025， 11（27）： eadu3739.
24
WANG X， LIU H， YUE M W， et al. Nitrate maintains mitochondrial membrane integrity by increasing Sialin-FKBP8 granules via liquid-liquid-phase separation［J］. Redox Biol， 2025， 88： 103901.
25
GELBERG H， HEALY L， WHITELEY H， et al. In vivo enzymatic removal of alpha 2： >6-linked sialic acid from the glomerular filtration barrier results in podocyte charge alteration and glomerular injury［J］. Lab Invest， 1996， 74（5）： 907-920.
26
CHOI S I， SIMONE J V， JORNEY L J. Neuraminidase-induced thrombocytopenia in rats［J］. Br J Haematol， 1972， 22（1）： 93-101.
27
KNOP J， AX W， SEDLACEK H H， et al. Effect of Vibriocholerae neuraminidase on the phagocytosis of E. coli by macrophages in vivo and in vitro［J］. Immunology， 1978， 34（3）： 555-563.
28
TOKORO Y， NAGAE M， NAKANO M， et al. LacdiNAc synthase B4GALNT3 has a unique PA14 domain and suppresses N-glycan capping［J］. J Biol Chem， 2024， 300（7）： 107450.
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doi: 10.16016/j.2097-0927.202602079
  • 接收时间：2026-02-15
  • 首发时间：2026-10-23
  • 出版时间：2026-05-15
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  • 收稿日期：2026-02-15
  • 修回日期：2026-03-12
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    1陆军军医大学（第三军医大学）第一附属医院骨科，重庆

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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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