Mesenchymal stem cell-derived exosomal microRNA-136-5p inhibits chondrocyte degeneration in traumatic osteoarthritis by targeting ELF3

Arthritis Research & Therapy

Junfeng Li¹  Yuanyuan Shi²  Xue Chen³  Jun Zhang³  Pan Xue³  Xinli Ma⁴ 

[1] Department of Clinical Laboratory, The Second Hospital of Jilin University, No. 218, Ziqiang Street, Nanguan District, 130041, Changchun, Jilin Province, People’s Republic of China;Department of Nursing, The Second Hospital of Jilin University, 130041, Changchun, People’s Republic of China;Department of Orthopedics, The Second Hospital of Jilin University, No. 218, Ziqiang Street, Nanguan District, 130041, Changchun, Jilin Province, People’s Republic of China;Intensive Care Unit, The Second Hospital of Jilin University, 130041, Changchun, People’s Republic of China;

关键词: Traumatic osteoarthritis;    Chondrocyte degeneration;    Bone marrow mesenchymal stem cells;    Exosome;    microRNA-136-5p;    ELF3;    Extracellular matrix secretion;    Migration;   

DOI  :  10.1186/s13075-020-02325-6

来源: Springer

【 摘 要 】

BackgroundEmerging evidence suggests that microRNAs (miRs) are associated with the progression of osteoarthritis (OA). In this study, the role of exosomal miR-136-5p derived from mesenchymal stem cells (MSCs) in OA progression is investigated and the potential therapeutic mechanism explored.MethodsBone marrow mesenchymal stem cells (BMMSCs) and their exosomes were isolated from patients and identified. The endocytosis of chondrocytes and the effects of exosome miR-136-5p on cartilage degradation were observed and examined by immunofluorescence and cartilage staining. Then, the targeting relationship between miR-136-5p and E74-like factor 3 (ELF3) was analyzed by dual-luciferase report assay. Based on gain- or loss-of-function experiments, the effects of exosomes and exosomal miR-136-5p on chondrocyte migration were examined by EdU and Transwell assay. Finally, a mouse model of post-traumatic OA was developed to evaluate effects of miR-136-5p on chondrocyte degeneration in vivo.ResultsIn the clinical samples of traumatic OA cartilage tissues, we detected increased ELF3 expression, and reduced miR-136-5p expression was determined. The BMMSC-derived exosomes showed an enriched level of miR-136-5p, which could be internalized by chondrocytes. The migration of chondrocyte was promoted by miR-136-5p, while collagen II, aggrecan, and SOX9 expression was increased and MMP-13 expression was reduced. miR-136-5p was verified to target ELF3 and could downregulate its expression. Moreover, the expression of ELF3 was reduced in chondrocytes after internalization of exosomes. In the mouse model of post-traumatic OA, exosomal miR-136-5p was found to reduce the degeneration of cartilage extracellular matrix.ConclusionThese data provide evidence that BMMSC-derived exosomal miR-136-5p could promote chondrocyte migration in vitro and inhibit cartilage degeneration in vivo, thereby inhibiting OA pathology, which highlighted the transfer of exosomal miR-136-5p as a promising therapeutic strategy for patients with OA.

【 授权许可】

CC BY