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
  • 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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