聚蛋白多糖酶
骨关节炎
软骨
软骨细胞
细胞生物学
合成代谢
分解代谢
透明软骨
平衡
生物
化学
医学
病理
内分泌学
解剖
生物化学
酶
关节软骨
替代医学
作者
Yun Zhang,Shuaijun Li,Peisheng Jin,Tao Shang,Ruizhu Sun,Liangyu Lu,Kaijin Guo,Jiping Liu,Yongjuan Tong,Junbang Wang,Sanhong Liu,Chen Wang,Yubin Kang,Wenmin Zhu,Qian Wang,Xiaoren Zhang,Feng Yin,Yi Sun,Lei Cui
标识
DOI:10.1038/s41467-022-30119-8
摘要
Abstract Damaged hyaline cartilage has no capacity for self-healing, making osteoarthritis (OA) “difficult-to-treat”. Cartilage destruction is central to OA patho-etiology and is mediated by matrix degrading enzymes. Here we report decreased expression of miR-17 in osteoarthritic chondrocytes and its deficiency contributes to OA progression. Supplementation of exogenous miR-17 or its endogenous induction by growth differentiation factor 5, effectively prevented OA by simultaneously targeting pathological catabolic factors including matrix metallopeptidase-3/13 (MMP3/13), aggrecanase-2 (ADAMTS5), and nitric oxide synthase-2 (NOS2). Single-cell RNA sequencing of hyaline cartilage revealed two distinct superficial chondrocyte populations (C1/C2). C1 expressed physiological catabolic factors including MMP2, and C2 carries synovial features, together with C3 in the middle zone. MiR-17 is highly expressed in both superficial and middle chondrocytes under physiological conditions, and maintains the physiological catabolic and anabolic balance potentially by restricting HIF-1α signaling. Together, this study identified dual functions of miR-17 in maintaining cartilage homeostasis and prevention of OA.
科研通智能强力驱动
Strongly Powered by AbleSci AI