Authors: Yun Zhang, Shuaijun Li, Peisheng Jin, Ting Shang, Ruizhu Sun, Laiya Lu, Kaijin Guo, Jiping Liu, Yongjuan Tong, Junbang Wang, Sanhong Liu, Chen Wang, Yubin Kang, Wenmin Zhu, Qian Wang, Xiaoren Zhang, Feng Yin, Yi Eve Sun, Lei Cui
Published: 2022-05-04
DOI: 10.1038/s41467-022-30119-8
Source: Full article
AbstractDamaged 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.