miR-142-5p as a CXCR4-Targeted MicroRNA Attenuates SDF-1-Induced Chondrocyte Apoptosis and Cartilage Degradation via Inactivating MAPK Signaling Pathway

Abstract

Osteoarthritis (OA) is a chronic joint function disorder with characteristics of chondrocytes reduction and extracellular matrix (ECM) components destruction. MicroRNAs (miRNAs) and the SDF-1/CXCR4 axis are essential factors of chondrocyte apoptosis and ECM degeneration. However, very few studies have investigated the correlation between miRNAs and the SDF-1/CXCR4 axis in osteoarthritis so far. Here, through miRNAs microarray and bioinformatics analyses, we identified miR-142-5p as a CXCR4-targeted and dramatically downregulated miRNA in cartilage from OA patients, as well as in SDF-1-induced OA chondrocytes in vitro. In SDF-1-treated primary human OA chondrocytes that were transfected with a miR-142-5p mimic or inhibitor, the expression of CXCR4 was found to be inversely correlated with the expression of miR-142-5p. The dual luciferase reporter assay further verified the target relationship between miR-142-5p and CXCR4. Overexpression of miR-142-5p alleviated OA pathology by suppressing chondrocyte apoptosis, even in CXCR4 overexpressed OA chondrocytes. This was associated with decreased cartilage matrix degradation, reduced cartilage inflammation, and inactivated MAPK signaling pathway. Our study suggests that upregulated expression of CXCR4-targeted miR-142-5p can inhibit apoptosis, inflammation, and matrix catabolism and inactivate the MAPK signaling pathway in OA chondrocytes. Our work provides important insight into targeting miR-142-5p and the SDF-1/CXCR4 axis in OA therapy.

A novel method to establish the rabbit model of knee Osteoarthritis: Intra-articular Injection of SDF-1 induces OA

“…Other researchers also obtained the similar result as our experiment. By changing the content of SDF-1 in the joint, SDF-1/CXCR4 signaling pathway can be regulated, which affects the apoptosis of chondrocyte, and in ammation, and matrix Catabolism [20,[28][29][30] The results of current research were all highly consistent with the predictions that exogenous SDF-1 intraarticular injection could establish the OA rabbit model. High dose of SDF-1 40ug/kg can cause the degeneration of rabbit knee joints faster, reaching middle stage of OA, and the e cacy similar to traditional surgical modeling.…”

Expression levels of CXCR4 and CXCL12 in patients with rheumatoid arthritis and its correlation with disease activity

“…CXCL12 can also be secreted and produced by joint synovial cells, while CXCR4 can be expressed on the surface of articular chondrocytes ( 14 , 15 ). The activation of CXCR4 and CXCL12 can induce the secretion of a variety of inflammatory factors from articular chondrocytes, leading to apoptosis and destruction of chondrocytes ( 16 , 17 ). Previous studies have demonstrated that CXCR4 and CXCL12 together can serve an important role in lupus erythematosus ( 18-20 ).…”

High-Throughput Sequencing Reveals CXCR4 and IGF1 Behave Different Roles in Weightlessness Osteoporosis

“…Studies [ 30 ] have shown that SDF-1/CXCR4 played a significant role in the occurrence and development of bone differentiation, bone regeneration, and orthopedic diseases, such as neovascularization, BMSC migration, and cytokine secretion. In addition, SDF-1/CXCR4 could also promote BMSCs bone regeneration and differentiation through MAPK signaling pathway [ 31 ]. However, our findings revealed that CXCR4 was highly expressed in weightlessness osteoporosis, which may contradict the low expression state in normal osteoporosis.…”