目的观察小鼠骨关节炎模型中关节软骨组织中基质金属蛋白酶13(matrix metalloproteinase 13,MMP-13)表达水平的变化,探讨其与关节损伤之间的关系。方法在小鼠原代软骨细胞培养中用IL-1β诱导炎症细胞外环境,采用RT-PCR检测MMP-13的表达水平。手术诱导不稳定的内侧半月板(destabilization of the medial meniscus,DMM)建立小鼠骨关节炎模型,观察术后5周和10周小鼠关节软骨组织变化情况,并用免疫组化检测MMP-13在受损的关节软骨中的表达。结果用IL-1β处理的原代软骨细胞中MMP-13的mRNA表达明显较高(P<0.01)。DMM术后小鼠关节软骨出现骨关节炎表现,且术后10周小鼠关节损伤程度较术后5周小鼠严重。免疫组化结果显示术后5周小鼠软骨组织中MMP-13的表达高于对照组;术后10周软骨组织中MMP-13进一步增高。结论在小鼠骨关节炎模型发病过程中,MMP-13作为一个具有软骨破坏性的标志分子在关节软骨中持续高表达,在骨关节炎发生过程中起重要作用。
Fibroblast growth factor （FGF）/fibroblast growth factor receptor （FGFR） signaling plays essential roles in bone development and diseases. Missense mutations in FGFs and FGFRs in humans can cause various congenital bone diseases, including chondrodysplasia syndromes, craniosynostosis syndromes and syndromes with dysregulated phosphate metabolism. FGF/FGFR signaling is also an important pathway involved in the maintenance of adult bone homeostasis. Multiple kinds of mouse models, mimicking human skeleton diseases caused by missense mutations in FGFs and FGFRs, have been established by knock-m/out and transgenic technologies. These genetically modified mice provide good models for studying the role of FGF/FGFR signaling in skeleton development and homeostasis. In this review, we summarize the mouse models of FGF signaling-related skeleton diseases and recent progresses regarding the molecular mechanisms, underlying the role of FGFs/FGFRs in the regulation of bone development and homeostasis. This review also provides a perspective view on future works to explore the roles of FGF signaling in skeletal development and homeostasis.
