2. Academic Validation
  3. Dual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis

Dual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis

  • Nat Commun. 2022 May 4;13(1):2447. doi: 10.1038/s41467-022-30119-8.
Yun Zhang 1,  Shuaijun Li 2,  Peisheng Jin 3,  Ting Shang 4,  Ruizhu Sun 2,  Laiya Lu 1,  Kaijin Guo 5,  Jiping Liu 1,  Yongjuan Tong 4,  Junbang Wang 6,  Sanhong Liu 7,  Chen Wang 7,  Yubin Kang 4,  Wenmin Zhu 1,  Qian Wang 2,  Xiaoren Zhang 8,  Feng Yin 1,  Yi Eve Sun 9,  Lei Cui 10 11 12
Affiliations

Affiliations

  • 1 Shanghai Institute of Stem Cell Research and Clinical Translation & Institute for Regenerative Medicine & Department of Joint Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
  • 2 Key Laboratory of spine and spinal cord injury repair and regeneration, Ministry of Education of the People's Republic of China & Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
  • 3 Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • 4 Department of Plastic Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
  • 5 Department of Orthopedics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • 6 Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
  • 7 Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.
  • 8 Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
  • 9 Shanghai Institute of Stem Cell Research and Clinical Translation & Institute for Regenerative Medicine & Department of Joint Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. [email protected].
  • 10 Shanghai Institute of Stem Cell Research and Clinical Translation & Institute for Regenerative Medicine & Department of Joint Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. [email protected].
  • 11 Key Laboratory of spine and spinal cord injury repair and regeneration, Ministry of Education of the People's Republic of China & Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Shanghai, China. [email protected].
  • 12 Department of Plastic Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China. [email protected].
PMID: 35508470 DOI: 10.1038/s41467-022-30119-8
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.

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