MicroRNA‐210‐3p Promotes Chondrogenic Differentiation and Inhibits Adipogenic Differentiation Correlated with HIF‐3α Signalling in Bone Marrow Mesenchymal Stem Cells

Abstract

Cartilage injury of the knee joint is very common. Due to the limited self-healing ability of articular cartilage, osteoarthritis is very likely to occur if left untreated. Bone marrow mesenchymal stem cells (BMMSCs) are widely used in the study of cartilage injury due to their low immunity and good amplification ability, but they still have disadvantages, such as heterogeneous undifferentiated cells. MicroRNAs can regulate the chondrogenic differentiation ability of MSCs by inhibiting or promoting mRNA translation and degradation. In this research, we primarily investigated the effect of microRNA-210-3p (miR-210-3p) on chondrogenic and adipogenic differentiation of BMMSCs in vitro. Our results demonstrate that miR-210-3p promoted chondrogenic differentiation and inhibited adipogenic differentiation of rat BMMSCs, which was related to the HIF-3α signalling pathway. Additionally, miR-210-3p promotes mRNA and protein levels of the chondrogenic expression genes COLII and SOX9 and inhibits mRNA and protein levels of the adipogenic expression genes PPARγ and LPL. Thus, miR-210-3p combined with BMMSCs is a candidate for future clinical applications in cartilage regeneration and could represent a promising new therapeutic target for OA.

Engineering exosomes by three-dimensional porous scaffold culture of human umbilical cord mesenchymal stem cells promote osteochondral repair

“… miRNA Up/down Previously reported studies Ref. miR-127–5p up targets WNT5A, enhances chondrogenesis [ 23 ] miR-210 up upregulates Col2 and Sox9 expression，targets Runx3 to promote proliferation, migration [ 24 , 25 ] miR-29a-3p up upregulates the expression of Sox 9, Col-2a1, and aggrecan，promotes macrophage polarization to the M2 subtype [ 26 , 27 ] miR-30a down downregulation of Sox9 promotes extracellular matrix degradation [ 28 ] miR-320 up targets MMP-13 and regulates chondrogenesis [ 29 ] miR-328–3p up increases chondrocyte viability and attenuates chondrocyte apoptosis and ECM degradation [ 30 ] miR-574–3p down RXRα downregulation [ 31 ] miR-125a-3p up Inhibits TLR and NFκΒ signaling to switch macrophages to the M2 phenotype [ 32 ] miR-125a-5p up diminishes M1 phenotype expression induced by LPS and promotes M2 marker expression induced by IL-4 [ 33 ] miR-155–5p down promotes macrophage M1 polarization and Inhibits polarization of macrophages to the M2 type [ 34 ] miR-21–5p Up reduces apoptosis and promotes macrophage M2 polarization; enhances the proliferation of MSCs [ [35] , [36] , [37] ] let-7d-3p down inhibits intratumoral macrophage M2 polarization ...…”

MicroRNA as Possible Mediators of the Synergistic Effect of Celecoxib and Glucosamine Sulfate in Human Osteoarthritic Chondrocyte Exposed to IL-1β

“…In addition, miR-210 was found to be associated to OA due to its higher levels in synovial fluid of patients with knee OA compared to healthy individuals [67]. Furthermore, miR-210 contribute to chondrogenic differentiation, DNA damage response, and apoptosis in bone marrow mesenchymal stem cells and synovial fibroblasts [68,69].…”

Single‑cell sequencing, genetics, and epigenetics reveal mesenchymal stem cell senescence in osteoarthritis (Review)

“…During cartilage differentiation of hADMSCs, the expression of SOX9 is gradually upregulated over time ( 123 ). miR-210-3p promotes cartilage differentiation of rat BMSCs and promotes mRNA and protein levels of cartilage expression genes COL2 and SOX9 ( 124 ). miR-130b inhibitors induce chondrocyte differentiation and chondrocyte growth of BMSCs by targeting SOX9 ( 125 ).…”