miR-24 Attenuates IL-1β-Induced IL-6 Upregulation in Temporomandibular Joint Synovium-Derived Mesenchymal Stem Cells
TL;DR
A role for the miR-24–MARK4 axis in modulating inflammatory responses in SMSCs is supported in modulating inflammatory responses in SMSCs and provide a basis for further preclinical investigation.
Abstract
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. The role of microRNA-24 (miR-24) in the development of temporomandibular joint (TMJ) OA remains unclear. To address this, the ability of miR-24 to attenuate inflammatory responses induced by interleukin-1β (IL-1β) in synovium-derived mesenchymal stem cells (SMSCs) by targeting microtubule affinity regulating kinase 4 (MARK4) was investigated. Exploratory analyses of synovial tissues from eight patients with TMJ OA showed a positive association between IL-1β and IL-6 and an inverse association between miR-24 and IL-1β. Overexpression of miR-24 inhibited IL-6 upregulation and nuclear factor-κB (NF-κB) pathway activation induced by IL-1β. Bioinformatics analysis and dual-luciferase assays identified MARK4 as a direct target of miR-24. The knockdown of MARK4 inhibited IL-6 upregulation of SMSCs induced by IL-1β. In a preclinical rat model of TMJ OA, intra-articular delivery of miR-24 agomir was associated with changes in inflammatory and cartilage-related gene expression. These results support a role for the miR-24–MARK4 axis in modulating inflammatory responses in SMSCs and provide a basis for further preclinical investigation.