2. Academic Validation
  3. miR-140 Attenuates the Progression of Early-Stage Osteoarthritis by Retarding Chondrocyte Senescence

miR-140 Attenuates the Progression of Early-Stage Osteoarthritis by Retarding Chondrocyte Senescence

  • Mol Ther Nucleic Acids. 2020 Mar 6;19:15-30. doi: 10.1016/j.omtn.2019.10.032.
Hai-Bo Si 1,  Ti-Min Yang 2,  Lan Li 3,  Mei Tian 4,  Li Zhou 5,  Dai-Ping Li 6,  Qiang Huang 6,  Peng-de Kang 6,  Jing Yang 6,  Zong-Ke Zhou 6,  Jing-Qiu Cheng 3,  Bin Shen 7
Affiliations

Affiliations

  • 1 Department of Orthopaedics and National Clinical Research Centre for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 2 Department of Orthopaedics and National Clinical Research Centre for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Orthopaedics, Tibet Autonomous Region People's Hospital, Lasa 850000, China.
  • 3 Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 4 Department of Ultrasound, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 5 Research Core Facility, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 6 Department of Orthopaedics and National Clinical Research Centre for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 7 Department of Orthopaedics and National Clinical Research Centre for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: shenbin_1971@163.com.
PMID: 31790972 DOI: 10.1016/j.omtn.2019.10.032
Abstract

Osteoarthritis (OA) is a major cause of joint pain and disability, and chondrocyte senescence is a key pathological process in OA and may be a target of new therapeutics. MicroRNA-140 (miR-140) plays a protective role in OA, but little is known about its epigenetic effect on chondrocyte senescence. In this study, we first validated the features of chondrocyte senescence characterized by increased cell cycle arrest in the G0/G1 phase and the expression of senescence-associated β-galactosidase (SA-βGal), p16INK4a, p21, p53, and γH2AX in human knee OA. Then, we revealed in interleukin 1β (IL-1β)-induced OA chondrocytes in vitro that pretransfection with miR-140 effectively inhibited the expression of SA-βGal, p16INK4a, p21, p53, and γH2AX. Furthermore, in vivo results from trauma-induced early-stage OA rats showed that intra-articularly injected miR-140 could rapidly reach the chondrocyte cytoplasm and induce molecular changes similar to the in vitro results, resulting in a noticeable alleviation of OA progression. Finally, bioinformatics analysis predicted the potential targets of miR-140 and a mechanistic network by which miR-140 regulates chondrocyte senescence. Collectively, miR-140 can effectively attenuate the progression of early-stage OA by retarding chondrocyte senescence, contributing new evidence of the involvement of miR-mediated epigenetic regulation of chondrocyte senescence in OA pathogenesis.

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