促进老年退行性骨关节炎软骨内源性修复的化合物研究进展

老年退行性骨关节炎(OA)是由关节损伤、肥胖和衰老等因素引起的一种退行性疾病,最终引起关节软骨损伤,导致运动功能障碍。软骨细胞及细胞外基质是软骨组织的主要成分,它们的损伤是引起OA的根本原因。目前OA的治疗仅限于缓解症状,而随着干细胞的发现及对软骨细胞的深入认识,开发增强软骨内源性修复的药物是OA治疗的重要方向。目前研究发现,kartogenin等化合物可以促进间充质干细胞选择性的分化为软骨细胞而起到修复作用,此外,一些化合物还可以调控软骨细胞的信号通路,起到促进软骨细胞增殖、抑制软骨细胞凋亡、抑制基质金属蛋白酶活性、增加细胞外基质合成等作用,从而维持软骨细胞的数量、促进软骨基质的合成而抑制其降解。这些方法比常规通过微创刺激内源性干细胞或移植自体细胞更加安全、有效。本文就化合物对促进老年退行性骨炎软骨内源性修复的研究进行综述,为发现更多的有效化合物提供基础。

Progress of Compounds Promoting Endogenous Repair of Cartilage in Osteoarthritis

ABSTRACT: Osteoarthritis (OA) is a degenerative disease caused by joint damage, obesity and aging. OA can cause articular cartilage damage and motor dysfunction. Cartilage injury is the main reason of OA due to the key role of chondrocytes and extracellular matrix (ECM) in cartilage. The current treatment of OA is limited to symptomatic relief. However, more studies about stem cells and chondro- cytes provides many evidences of enhancing endogenous cartilage repair, which is an important method of OA treatment. Compounds can promote the specific differentiation of mesenchymal stem cells to chondrocytes. In addition, the compounds can also promote chon- drocyte proliferation, inhibit chondrocyte apoptosis, inhibit matrix metalloproteinase activity and increase ECM synthesis by regulating multiple signal pathways, which play important role in maintaining the number of chondrocytes, promoting the ECM synthesis and inhi- biting ECM degradation. These methods are safer and more effective than the stimulation of endogenous stem cells or autologous cells by minimally invasive procedures. So, this review summarizes the studies about compounds that promote cartilage endogenous repair of se- nile degenerative osteitis, and provides the basis for finding more effective compounds.