Article(id=1208791318453678119, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208791311621157694, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2021.11.15, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1614873600000, receivedDateStr=2021-03-05, revisedDate=1627401600000, revisedDateStr=2021-07-28, acceptedDate=null, acceptedDateStr=null, onlineDate=1766127908576, onlineDateStr=2025-12-19, pubDate=1638028800000, pubDateStr=2021-11-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766127908576, onlineIssueDateStr=2025-12-19, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766127908576, creator=13701087609, updateTime=1766127908576, updator=13701087609, issue=Issue{id=1208791311621157694, tenantId=1146029695717560320, journalId=1189873630562394117, year='2021', volume='46', issue='11', pageStart='1061', pageEnd='1164', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1766127906946, creator=13701087609, updateTime=1766128932678, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1208795613920104935, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208791311621157694, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1208795613920104936, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208791311621157694, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1153, endPage=1158, ext={EN=ArticleExt(id=1208791318902468663, articleId=1208791318453678119, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Research progress on the role of SDF-1/CXCR4 in intervertebral disc degeneration, columnId=1190243275882729994, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Low back pain has become a public health problem worldwide. Intervertebral disc degeneration (IDD) is the main cause of low back pain, however, the molecular mechanism of IDD has not been fully elucidated. Stromal cell-derived factor-1(SDF-1) and its receptor C-X-C motif chemokine receptor-4 (CXCR4) are highly expressed in degenerative disc tissues and are believed to mediate the occurrence and development of IDD, including disc angiogenesis, inflammatory response, stromal cell metabolism, apoptosis and other pathological processes. In recent years, SDF-1/CXCR4 have also been used in tissue engineering research such as disc regeneration. Therefore, actively exploring the role of SDF-1/CXCR4 in IDD is of great significance for elucidating the molecular mechanism of IDD and studying new strategies for the treatment of IDD. The research progress in recent years has been reviewed in present paper of SDF-1/CXCR4 in IDD and intervertebral disc regeneration, in order to provide a basis for intensive study of the molecular mechanism of IDD and provide new ideas for early targeted treatment of IDD.

, correspAuthors=Xiao-Qi Liu, authorNote=null, correspAuthorsNote=
*E-mail:
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下腰痛已成为全球公共健康问题,椎间盘退变(IDD)是引发腰痛的最主要原因,然而IDD的分子机制仍未完全阐明。基质细胞源性因子-1(SDF-1)及其受体CXCR4在退变的椎间盘组织中高表达,被认为可介导IDD的发生和发展,如间盘血管再生、炎症反应、基质细胞代谢、细胞凋亡等病理过程,近年来还被应用于椎间盘再生等组织工程研究中。因此,积极探索SDF-1/CXCR4在IDD中的作用对于阐明IDD的分子机制及探寻治疗IDD的新策略具有重要意义。该文就近年来SDF-1/CXCR4在IDD及椎间盘再生中的作用研究进展进行综述,以期为深入了解IDD的分子机制提供依据,同时为早期靶向治疗IDD提供新的思路。

, correspAuthors=刘晓奇, authorNote=null, correspAuthorsNote=
刘晓奇,E-mail:
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SDF-1/CXCR4在椎间盘退变中的作用研究进展
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郝海静 1 , 王浩辉 1 , 闫新星 1 , 李世文 1 , 徐璐 2 , 刘晓奇 1, *
解放军医学杂志 | 综述 2021,46(11): 1153-1158
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解放军医学杂志 | 综述 2021, 46(11): 1153-1158
SDF-1/CXCR4在椎间盘退变中的作用研究进展
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郝海静1, 王浩辉1, 闫新星1, 李世文1, 徐璐2, 刘晓奇1, *
作者信息
  • 1哈尔滨医科大学附属第二医院骨科,哈尔滨 150001
  • 2哈尔滨医科大学附属第二医院神经内科,哈尔滨 150001
  • 郝海静,硕士研究生,主要从事脊柱外科及骨组织工程方面的研究

通讯作者:

刘晓奇,E-mail:
Research progress on the role of SDF-1/CXCR4 in intervertebral disc degeneration
Hai-Jing Hao1, Hao-Hui Wang1, Xin-Xing Yan1, Shi-Wen Li1, Lu Xu2, Xiao-Qi Liu1, *
Affiliations
  • 1Department of Orthopedics, the Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China
  • 2Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China
出版时间: 2021-11-28 doi: 10.11855/j.issn.0577-7402.2021.11.15
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下腰痛已成为全球公共健康问题,椎间盘退变(IDD)是引发腰痛的最主要原因,然而IDD的分子机制仍未完全阐明。基质细胞源性因子-1(SDF-1)及其受体CXCR4在退变的椎间盘组织中高表达,被认为可介导IDD的发生和发展,如间盘血管再生、炎症反应、基质细胞代谢、细胞凋亡等病理过程,近年来还被应用于椎间盘再生等组织工程研究中。因此,积极探索SDF-1/CXCR4在IDD中的作用对于阐明IDD的分子机制及探寻治疗IDD的新策略具有重要意义。该文就近年来SDF-1/CXCR4在IDD及椎间盘再生中的作用研究进展进行综述,以期为深入了解IDD的分子机制提供依据,同时为早期靶向治疗IDD提供新的思路。

基质细胞源性因子-1  /  椎间盘退变  /  血管再生  /  椎间盘再生

Low back pain has become a public health problem worldwide. Intervertebral disc degeneration (IDD) is the main cause of low back pain, however, the molecular mechanism of IDD has not been fully elucidated. Stromal cell-derived factor-1(SDF-1) and its receptor C-X-C motif chemokine receptor-4 (CXCR4) are highly expressed in degenerative disc tissues and are believed to mediate the occurrence and development of IDD, including disc angiogenesis, inflammatory response, stromal cell metabolism, apoptosis and other pathological processes. In recent years, SDF-1/CXCR4 have also been used in tissue engineering research such as disc regeneration. Therefore, actively exploring the role of SDF-1/CXCR4 in IDD is of great significance for elucidating the molecular mechanism of IDD and studying new strategies for the treatment of IDD. The research progress in recent years has been reviewed in present paper of SDF-1/CXCR4 in IDD and intervertebral disc regeneration, in order to provide a basis for intensive study of the molecular mechanism of IDD and provide new ideas for early targeted treatment of IDD.

stromal cell-derived factor-1  /  intervertebral disc degeneration  /  angiogenesis  /  intervertebral disc regeneration
郝海静, 王浩辉, 闫新星, 李世文, 徐璐, 刘晓奇. SDF-1/CXCR4在椎间盘退变中的作用研究进展. 解放军医学杂志, 2021 , 46 (11) : 1153 -1158 . DOI: 10.11855/j.issn.0577-7402.2021.11.15
Hai-Jing Hao, Hao-Hui Wang, Xin-Xing Yan, Shi-Wen Li, Lu Xu, Xiao-Qi Liu. Research progress on the role of SDF-1/CXCR4 in intervertebral disc degeneration[J]. Medical Journal of Chinese People’s Liberation Army, 2021 , 46 (11) : 1153 -1158 . DOI: 10.11855/j.issn.0577-7402.2021.11.15
全球约有6.37亿人受到下腰痛的影响[1],下腰痛在增加患者身心痛苦的同时,也给社会带来巨大的医疗和经济负担[2]。椎间盘退变(intervertebral disc degeneration,IDD)被认为是导致腰痛的最主要原因,已成为全球性的公共健康问题[3],临床主要表现为纤维组织变性、椎间盘高度降低、纤维环破裂、软骨终板缺失、环状纤维黏液性变、小关节突骨赘形成及椎间盘钙化等[4-5]。多种细胞活动如炎症反应、细胞凋亡和基质新陈代谢失衡等参与了IDD的发生[6-7]。趋化因子是一类分子质量为7~15 ku的可溶性小细胞因子,在一定的生理和病理条件下,具有引导免疫细胞在指定位置趋化的能力[8]。依据趋化因子N末端2个半胱氨酸的位置状态不同,趋化因子可分为4个亚类,即CXC类(插入1个氨基酸残基)、CC类(不插入氨基酸残基)、C类(N端只有1个氨基酸)和C3XC类(插入3个氨基酸残基),而基质细胞源性因子-1(stromal cell-derived factor-1,SDF-1)属于CXC类趋化因子,其基因编码序列位于10q11.1,开放读码框为270 bp,由68个氨基酸构成[9]。CXC亚家族的趋化因子参与中性粒细胞的趋化,是广为人且和研究最广泛的趋化因子[10]。SDF-1最早从骨髓间充质干细胞中提取出来,可与G蛋白偶联受体C-X-C序列的趋化因子受体4(C-X-C motif chemokine receptor-4,CXCR4)结合而激活不同类型的细胞,并影响血管生成和白细胞运输[11-12]。SDF-1/CXCR4轴参与多种病理过程,包括肿瘤、自身免疫疾病和炎症性疾病等[13-14]。近年来大量研究证实,SDF-1/CXCR4在IDD中发挥重要作用,有望成为早期诊断IDD的敏感生物标志物和延缓甚至逆转IDD的有效靶点。本文就SDF-1/CXCR4在IDD中的作用研究进展进行综述,旨在为深入研究IDD提供新的思路。
椎间盘是一个适度活动的关节,其将脊柱的椎骨分开,主要为脊柱提供灵活性,并允许大范围的运动和机械负荷的传递[15]。椎间盘主要由软骨终板、纤维环和髓核组成[16],其中软骨终板位于椎间盘上部和下部与椎体交界处,可将椎间盘固定在椎体之上;纤维环的结构厚而致密,可分为外环和内环,外环由紧密排列的同心片层状胶原组织构成,主要由产生Ⅰ型胶原(collagen-Ⅰ,COL-Ⅰ)的成纤维细胞组成;内环多为包含COL-Ⅰ和Ⅱ型胶原(collagen-Ⅱ,COL-Ⅱ)的纤维软骨;髓核被包围在纤维环中,在生理情况下为凝胶状,主要由蛋白多糖和COL-Ⅱ形成的疏松网状结构组成[17]。由此可见,椎间盘主要由细胞外基质(extracellular matrix,ECM)如COL、蛋白多糖和其他基质蛋白组成,这些分子被局部现有的蛋白酶持续合成和降解,以维持椎间盘的稳态[18]
椎间盘长期处在低氧、低pH、高渗透压和应力波动的恶劣环境中[19]。随着椎间盘内细胞营养的减少、细胞废物的积累及ECM分子的降解,椎间盘内环境稳态失衡,形成一种酸性越来越强的环境,细胞活力被损害,进而引发炎症反应、细胞凋亡、ECM代谢失衡等病理过程,最终导致IDD[20]。与此同时,椎间盘的独特结构可将髓核从宿主免疫系统中分离出来,椎间盘中表达的免疫抑制分子对免疫细胞和细胞因子的浸润有抑制作用。因此,椎间盘被认为是免疫豁免器官,免疫豁免状态的稳定是维持椎间盘免疫系统稳态的基础,纤维环、软骨终板及免疫抑制分子共同组成了血液-髓核屏障,当该屏障受损时,髓核的自身免疫反应可激活各种下游级联反应,从而介导IDD的发生[21]
已经证实,SDF-1/CXCR4在椎间盘中表达且在退变的椎间盘中高表达。Zhang等[22]发现,SDF-1在椎体-软骨终板连接区域的骨髓来源细胞(bone marrow-derived cells,BMCs)和纤维环外层成纤维细胞中高表达,CXCR4在软骨终板细胞和髓核细胞中高表达。SDF-1结合CXCR4是一种互补蛋白表达模式,这种模式提示了一种旁分泌调节机制,即BMCs和成纤维细胞产生SDF-1,可在软骨终板细胞和髓核细胞附近发出信号CXCR4,从而介导趋化、造血、血管生成,以及肿瘤的扩散和转移等[23]。Er等[24]对比145例IDD患者和130名健康人的血清SDF-1水平发现,IDD患者血清SDF-1水平明显升高,且与Pfirrmann分级和多裂肌退行性变程度呈正相关,提示SDF-1可作为IDD早中期的生物标志物。总之,SDF-1/CXCR4在IDD中高表达,但在其他脊柱退变相关疾病如后纵韧带骨化、椎管狭窄等中的表达情况尚需进一步研究;值得注意的是,Modic改变作为评价软骨终板退变的常用指标,其与SDF-1/CXCR4表达的关系有待阐明。
作为全身最大的无血管器官,椎间盘新生血管长入被认为是IDD的重要标志之一[25]。在椎间盘发生退变的过程中,椎间盘内部成分改变引起其力学性质的变化,当超过椎间盘承受负荷能力时,纤维环裂隙形成,随后肉芽组织和新血管在裂缝中生长。血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)的表达与椎间盘突出后血管形成密切相关[26]。作为一种内皮特异性有丝分裂原,VEGF通过动员骨髓来源的内皮祖细胞(endothelial progenitor cells,EPCs)和刺激血管内皮细胞(vascular endothelial cells,VECs)的增殖而在新生血管形成中发挥重要作用[27]。SDF-1与VEGF的相互调节可促进毛细血管的形成[28]。Jia等[29]的研究发现,SDF-1与VEGF在各型突出椎间盘的软骨终板中均呈高表达,尤其是“突出型”和“脱出型”,且二者的表达水平呈高度正相关,提示SDF-1与VEGF可能在软骨终板细胞的募集和椎间盘突出组织的血管化过程中发挥重要作用;Zhang等[30]研究发现,随着髓核细胞中SDF-1表达的增加,VECs的增殖迁移能力、管状结构形成能力增强,表明椎间盘血管化程度与IDD的严重程度呈正相关;Zhang等[31]进一步研究发现,IDD形成过程中髓核细胞可通过SDF-1/CXCR4轴来诱导VECs的成血管活动,并且这一活动在VECs内可能被PI3K/AKT通路调控。此外,有研究发现,突出的椎间盘可因新生血管的长入而被重吸收,进而使压迫症状减轻,但IDD中血管形成为炎性细胞因子和代谢相关蛋白酶提供了血管途径[32],可改变椎间盘正常营养供应及结构的完整性,且可能与IDD晚期的椎间盘钙化有关[33]。此外,神经生长因子诱导的痛觉纤维也可随新生血管长入椎间盘内部,同时携带炎性细胞因子,从而引发腰痛[34]。总之,椎间盘血管化既是IDD的始动因素,也贯穿IDD的全过程。SDF-1/CXCR4在IDD血管形成中发挥重要作用,有效靶向抑制SDF-1/CXCR4可能为治疗IDD提供新的方向,值得深入研究。然而,目前SDF-1/CXCR4介导椎间盘突出钙化及痛觉纤维长入的机制研究较少,值得进一步探索与阐明。
炎症反应与IDD关系密切[18]。核因子-κB(nuclear factor-κB,NF-κB)和丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPKs)通路蛋白被认为是骨骼肌肉系统疾病中炎症反应及分解代谢的主要调节因子,多项研究支持炎症反应介导了NF-κB或MAPKs通路在IDD中的作用[35]。近年来,SDF-1/CXCR4与NF-κB或MAPKs通路在IDD中的作用逐渐受到了关注。
NF-κB通路是各类细胞应对损伤、应激反应和炎症反应的共同通路[36]。NF-κB蛋白属于一个结构相关的快速作用转录因子家族,该家族成员都拥有一个共同的高度保守的300个氨基酸区域,即Rel同源结构域(Rel homology domain,RHD)。NF-κB家族有5个成员,分别为RelA(p65)、c-Rel、RelB、p50和p52,在哺乳动物中广泛表达[37]。有研究发现,NF-κB信号在人退变的椎间盘特别是髓核组织中被激活[38]。刘宗超等[39]通过小干扰RNA(small interfering RNA,siRNA)敲除CXCR4(CXCR4-siRNA),并利用NF-κB抑制剂吡咯烷二硫氨基甲酸酯(pyrrolidine dithiocarbamate,PDTC)研究SDF-1与NF-κB信号通路的关系,发现上调SDF-1的表达可增高髓核细胞的凋亡水平,但CXCR4敲除后髓核细胞凋亡水平降低;激活SDF-1可增高磷酸化NF-κB亚基p65的水平,而CXCR4敲除和PDTC处理后p65水平下调,提示SDF-1/CXCR4可能通过NF-κB通路促进髓核细胞凋亡而加重IDD。此外,独活寄生汤作为传统中医经典方剂,被证实可靶向下调SDF-1/CXCR4/NF-κB通路中多种蛋白的表达,从而抑制IDD中炎性介质的释放及椎间盘中EMC的降解,达到延缓甚至治疗IDD的目的[40]。MAPKs是一个高度保守的信号传导通路家族,能够促进体内激素、生长因子、炎性细胞因子等的激活[41]。MAPKs有3个主要亚家族:细胞外信号调节激酶(extracellular signal-regulated kinases,ERK)、c-Jun氨基末端激酶(c-Jun N-terminal kinases,JNKs)和p38亚型(p38MAPKs)[42]。大量研究证实,MAPKs在IDD中发挥着重要作用[43],但SDF-1是否介导MAPKs参与IDD有待进一步验证。Xiang等[44]发现,过表达CXCR4可激活MAPKs信号通路,而上调miR-142-5p可明显降低CXCR4的表达,进而抑制骨关节炎(osteoarthritis,OA)软骨细胞的凋亡、炎症反应和基质分解代谢,并使MAPKs信号通路失活。由于OA与IDD在形态及发病过程中存在许多相似之处,SDF-1与MAPKs在IDD中的作用值得进一步深入研究。此外,Zhang等[45]发现,SDF-1可以剂量依赖的方式上调基质金属蛋白酶(matrix metalloproteinase,MMP)1、2、3、9、13的表达,参与软骨终板中EMC的降解而导致软骨终板破裂,进而加重IDD,这一过程是否通过MAPKs相关通路介导有待进一步研究。
总之,SDF-1/CXCR4可能通过介导NF-κB和MAPKs通路参与IDD的发生和发展,然而,NF-κB与MAPKs是否存在共同通路介导IDD有待进一步研究,笔者推测NF-κB和MAPKs可能分别介导IDD的不同时期,且可能受SDF-1/CXCR4在不同时期表达量的影响;SDF-1/CXCR4与NF-κB家族的5种亚型、MAPKs的3种亚型之间的作用机制有待深入阐明;SDF-1/CXCR4与IDD相关细胞信号通路如刺猬蛋白、Wnt/β-catenin、Notch及PI3K/Akt等的调控关系研究较少,今后可将其作为探寻IDD分子机制及延缓IDD高效靶点的新的研究方向。
目前,IDD的治疗方法主要包括手术治疗和非手术治疗,但效果均不理想。新的方法如基因治疗、生长因子注射、干细胞治疗等组织工程方法正在开发中,以期促进椎间盘的再生[46]。SDF-1是一种具有造血干细胞功能的趋化因子,在组织受损时,干细胞从骨髓中被SDF-1招募,参与组织修复[47]。近年来,SDF-1/CXCR4在调控以干细胞为基础的各种椎间盘再生策略中发挥了重要作用。
Wei等[48]通过慢病毒转染产生过表达CXCR4的间充质干细胞(CXCR4-MSCs),用SPIO标记并移植入经环形穿刺诱导的兔变性椎间盘中,结果显示,CXCR4-MSCs能够促使MSCs向SDF-1迁移,致使Aggrecan、COL-Ⅱ mRNA表达增加,且移植后的椎间盘中SPIO阳性细胞增多,提示CXCR4过表达促进了MSCs在椎间盘中的滞留,从而减缓了椎间盘的高度丧失;Liu等[49]发现,将MSCs与髓核干细胞(nucleus pulposus-derived stem cells,NPSCs)共培养可导致髓核细胞的机械模量(弹性模量、松弛模量和瞬时模量)明显降低,生物活性(基质基因的增殖和表达)明显增加,而使用AMD3100抑制SDF-1或敲除NPSCs中的CXCR4可消除此作用;Ying等[50]发现,SDF-1的表达水平在体外培养的促炎细胞因子(如IL-1β和TNF-α)诱导间盘细胞模拟IDD的环境中明显上调,并以剂量依赖的方式增强NPSCs的迁移能力;同时SDF-1可增加CXCR4的表达,并刺激CXCR4从细胞质向细胞膜移位及细胞骨架重排。软骨终板干细胞(cartilage endplate stem cells,CESCs)也具备诱导髓核细胞再生的潜力,He等[51]发现,SDF-1在CESCs中高表达,而CXCR4则在NPSCs中高表达,将CESCs与NPSCs共培养(1:1)可有效促进NPCs的增殖。值得注意的是,这一过程可能是由SDF-1/CXCR4介导ERK1/2信号通路以旁分泌途径完成的,提示ERK1/2信号通路可能是IDD的保护通路,这与既往观念相反,因此深入研究SDF-1/CXCR4与ERK1/2通路在IDD中的作用,有望为椎间盘再生提供有效策略。此外,Zhang等[52]发现,将SDF-1注入椎间盘可能导致软骨终板退变,但SDF-1可使髓核中的EMC发生重构,从而保留更多的蛋白多糖基质密集区,促进髓核再生,表明SDF-1可能是促进CESCs向髓核归巢的有利因素。
IDD的特征之一是椎间盘细胞分解/合成代谢不平衡或椎间盘细胞死亡,从而导致ECM成分降解和水分流失。利用新细胞重新填充椎间盘可能有助于恢复组织稳态并延缓IDD进展。Pereira等[53]设计了一种负载耐热多聚透明质酸-N-异丙基丙烯酰胺(hyaluronan-poly N-isopropylacrylamide,HAP)的水凝胶并作为趋化剂释药系统,研究其在IDD中招募MSCs的潜力,结果显示,与仅用HAP处理的椎间盘相比,含SDF-1的HAP水凝胶显著增加了迁移到髓核切除椎间盘组织中MSCs的数量。该研究为开发基于内源性细胞迁移的IDD再生疗法提供了新的思路。Pereira等[54]将含有SDF-1(5 ng/ml)的透明质酸(HA)传递系统(HAPSDF5)注入髓核切除的牛椎间盘中,并将人MSCs接种于对侧软骨终板,结果显示,HAPSDF5增强了荧光标记的MSCs从软骨终板向椎间盘的迁移能力,此外,COL-Ⅱ的表达在较早的时间点即被检测到,表明HAPSDF5可通过增加COL-Ⅱ的产生而加速髓核中ECM的重塑。将SDF-1封装到纳米颗粒(nanoparticles,NPS)中是一种前景广阔的方法,Zhang等[52]以白蛋白/肝素NPS复合物(albumin/heparin complex nanoparticles,BHNPs)作为SDF-1的注射载体,发现BHNPs负载SDF-1可诱导MSCs迁移,且呈剂量依赖性,同时可增高Sox-9、Aggrecan及COL-Ⅱ mRNA和蛋白的表达水平,有效诱导纤维环及髓核再生。
总之,SDF-1/CXCR4通过发挥趋化和归巢作用介导MSCs、NPCs、CEPCs向椎间盘迁移及分化,促进椎间盘中EMC蛋白、髓核、纤维环的再生,进而改善椎间盘内环境,促进椎间盘再生。然而,SDF-1/CXCR4在此过程中是否存在诱发IDD的作用、SDF-1/CXCR4诱导椎间盘再生的最佳浓度及其毒性、SDF-1/CXCR4在椎间盘再生中的下游敏感通路等仍需深入研究。
IDD是一种成因及表现复杂,涉及各类椎间盘细胞、结构及功能改变的病理过程,了解IDD的分子机制和高效治疗靶点具有重要意义。SDF-1在IDD中同时扮演“敌”和“友”的角色,这可能与IDD的严重程度密切相关。在IDD早中期,一方面SDF-1协同VEGF促进椎间盘血管再生而调节椎间盘营养通路及新陈代谢的平衡,甚至使突出的椎间盘自发重吸收;另一方面,SDF-1还可动员和趋化MSCs、NPCc及EPCs,从而提高椎间盘再生效率。在IDD晚期,随着椎间盘血管化及炎症反应加重,椎间盘内环境严重失衡,SDF-1趋化退变相关蛋白信号通路等高表达,进一步加剧IDD,形成椎间盘内环境的恶性循环。然而,介导SDF-1在IDD中双重作用的具体分子机制仍未阐明,这可能与现有的研究方法缺乏晚期IDD动物模型等有关。依据IDD严重程度,在早中期靶向上调或在晚期下调SDF-1的表达可能是更为有效的IDD治疗策略,值得深入研究。
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2021年第46卷第11期
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doi: 10.11855/j.issn.0577-7402.2021.11.15
  • 接收时间:2021-03-05
  • 首发时间:2025-12-19
  • 出版时间:2021-11-28
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  • 收稿日期:2021-03-05
  • 修回日期:2021-07-28
基金
Heilongjiang Provincial Education Reform General Project(SJGY20190429)
黑龙江省教改一般项目(SJGY20190429)
Heilongjiang Provincial Education Reform General Project(SJGY20190430)
黑龙江省教改一般项目(SJGY20190430)
Horizontal Project of the Second Affiliated Hospital of Harbin Medical University(070500020146)
哈尔滨医科大学附属第二医院横向课题(070500020146)
Horizontal Project of the Second Affiliated Hospital of Harbin Medical University(070500020278)
哈尔滨医科大学附属第二医院横向课题(070500020278)
Standardized Training of Residents of the Second Affiliated Hospital of Harbin Medical University(2020020208)
哈尔滨医科大学附属第二医院住院医师规范化培训课题(2020020208)
Standardized Training of Residents of the Second Affiliated Hospital of Harbin Medical University(2020020223)
哈尔滨医科大学附属第二医院住院医师规范化培训课题(2020020223)
作者信息
    1哈尔滨医科大学附属第二医院骨科,哈尔滨 150001
    2哈尔滨医科大学附属第二医院神经内科,哈尔滨 150001

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

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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