MiR-24-3p attenuates IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting BCL2L12

Journal of Orthopaedic Surgery and Research

Ren Ding¹  Jin Xu¹  Xiaozhong Qian² 

[1] Department of Orthopedics, Baoshan District Shanghai Integrated Traditional Chinese and Western Medicine Hospital, No. 181 Youyi Road, Baoshan District, 201999, Shanghai, China;Department of Orthopedics, Shuguang Hospital Baoshan Branch, Shanghai University of Traditional Chinese Medicine, 201999, Shanghai, China;Department of Orthopedics, Community Health Center of Songnan Town, Baoshan District, 200441, Shanghai, China;

关键词: Chondrocytes;    Inflammation;    Osteoarthritis;    miR-24-3p;   

DOI  :  10.1186/s13018-021-02378-6

来源: Springer

【 摘 要 】

BackgroundMiR-24-3p has been reported to be involved in an osteoarthritis (OA)-resembling environment. However, the functional role and underlying mechanism of miR-24-3p in chondrocyte injury associated with OA remains unknown.MethodsThe expression of miR-24-3p was determined using reverse transcription quantitative PCR analysis in OA cases and control patients, as well as IL-1β-stimulated chondrocyte cell line CHON-001. The cell viability was analyzed by CCK-8 assay. Apoptosis status was assessed by caspase-3 activity detection. The pro-inflammatory cytokines (TNF-α and IL-18) were determined using ELISA assay. The association between miR-24-3p and B cell leukemia 2-like 12 (BCL2L12) was confirmed by luciferase reporter assay.ResultsWe first observed that miR-24-3p expression level was lower in the OA cases than in the control patients and IL-1β decreased the expression of miR-24-3p in the chondrocyte CHON-001. Functionally, overexpression of miR-24-3p significantly attenuated IL-1β-induced chondrocyte injury, as reflected by increased cell viability, decreased caspase-3 activity, and pro-inflammatory cytokines (TNF-α and IL-18). Western blot analysis showed that overexpression of miR-24-3p weakened IL-1β-induced cartilage degradation, as reflected by reduction of MMP13 (Matrix Metalloproteinase-13) and ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs-5) protein expression, as well as markedly elevation of COL2A1 (collagen type II). Importantly, BCL2L12 was demonstrated to be a target of miR-24-3p. BCL2L12 knockdown imitated, while overexpression significantly abrogated the protective effects of miR-24-3p against IL-1β-induced chondrocyte injury.ConclusionsIn conclusion, our work provides important insight into targeting miR-24-3p/BCL2L12 axis in OA therapy.

【 授权许可】

CC BY