Suppression of CRLF1 promotes the chondrogenic differentiation of bone marrow-derived mesenchymal stem and protects cartilage tissue from damage in osteoarthritis via activation of miR-320

Hao Xu,Changrong Ding,Cuicui Guo,Shuai Xiang,Hongfei Xiang,Bing Luo,Yingzhen Wang

doi:10.1186/s10020-021-00369-1

Hao Xu, Changrong Ding + Show 5 more

Open Access

https://doi.org/10.1186/s10020-021-00369-1

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Abstract

BackgroundOsteoarthritis (OA) is the most prevalent chronic joint disease, and is hard to be cured at present. Cytokine receptor-like factor 1 (CRLF1) has been identified as an upregulated gene in OA cartilage. However, the precise identities and functions of CRLF1 in OA progression have remained to be fully elucidated.MethodsWe used a murine model of injury-induced OA (destabilization of medial meniscus, DMM) and BMSCs to investigate the specific biological functions and mechanisms of CRLF1.ResultsWe found that CRLF1 was significantly increased in the DMM surgery-induced OA model and was down-regulated during chondrogenic differentiation of BMSCs. Luciferase reporter assays showed that CRLF1 was a direct target of miR-320 in BMSCs. miR-320 can reverse the effect of CRLF1 on cell proliferation, apoptosis and chondrogenic differentiation of BMSCs. Furthermore, knockdown of CRLF1 or over-expression of miR-320 can inhibit the apoptosis of primary chondrocytes.ConclusionSuppression of CRLF1 promotes the chondrogenic differentiation of BMSCs and protects cartilage tissue from damage in osteoarthritis via activation of miR-320.

Highlights

Osteoarthritis (OA) is the most prevalent chronic joint disease, and is hard to be cured at present
Cytokine receptor-like factor 1 (CRLF1) expression was higher in the Destabilization of medial meniscus (DMM) surgery‐induced OA mice model Eight weeks after the model was established, safranine O/solid green staining was performed, and the articular anatomical structure was divided into zones
The above findings suggested that the knockdown of CRLF1 or overexpression of miR-320 can inhibit the apoptosis of primary chondrocytes isolated from OA articular cartilage tissues in mice

Summary

Introduction

Osteoarthritis (OA) is the most prevalent chronic joint disease, and is hard to be cured at present. Cytokine receptor-like factor 1 (CRLF1) has been identified as an upregulated gene in OA cartilage. Osteoarthritis (OA) is a common musculoskeletal disease characterized by bone-cartilage homeostasis changes, leading to progressive degeneration of the synovial joint (Pereira et al 2011). Cytokine receptor-like factor 1 (CRLF1) is a soluble protein that is homologous with type I cytokine receptors. CRLF1 is reportedly highly expressed in damaged human knee osteoarthritic cartilage (Tew et al 2007) and involved in osteoarthritis downstream of TGF-beta (Tsuritani et al 2010). We attempted to investigate the expression of CRLF1 in cartilage tissues in mice with OA and explored the roles of CRLF1 in cell proliferation and chondrogenic differentiation of BMSCs. the possible molecular mechanism was investigated simultaneously and may be a useful therapeutic target

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