MiR-337-3p promotes chondrocytes proliferation and inhibits apoptosis by regulating PTEN/AKT axis in osteoarthritis.

Osteoarthritis (OA) is a degenerative disease of articular cartilage and its main pathological feature is cartilage destruction, but its specific pathogenesis is still debatable. The aim of this study was to explore the role of miR-337-3p in OA pathogenesis. The expression of miR-337-3p and PTEN in osteoarthritic cartilage tissues was detected using quantitative real time PCR and western blot, respectively. The regulation of miR-337-3p on PTEN was examined by luciferase reporter gene assays. The manipulation of miR-337-3p and PTEN was mediated by siRNA interference technology. The cell viability was analyzed by MTT assays. MiR-337-3p expression was significantly down-regulated in osteoarthritic cartilage tissues compared with normal cartilage tissues. Further studies confirmed that miR-337-3p overexpression evidently promoted the proliferation and inhibited the apoptosis of OA chondrocytes. PTEN expression was significantly up-regulated in osteoarthritic cartilage tissues and was negatively regulated by miR-337-3p in chondrocytes. PTEN silencing could improve the proliferation of OA chondrocytes and increased pAKT protein expression in OA chondrocytes. MiR-337-3p regulated OA chondrocytes proliferation through PTEN/AKT axis and thus involved in OA.

Huang Z ，Zhang N ，Ma W ，Dai X ，Liu J ... -  《-》

MiR-455-3p reduces apoptosis and alleviates degeneration of chondrocyte through regulating PI3K/AKT pathway.

This study aimed to explore the functions of miR-455-3p, PTEN, and PI3K/AKT pathway in osteoarthritis. We used the human bone marrow stem cell (BMSC), healthy chondrocytes, osteoarthritis chondrocytes (OA), and the IL-1β/TNF-α-treated chondrocyte model to explore the relationship between miR-455-3p and PTEN. Mimic or inhibitor was used to transfect chondrocytes to determine whether miR-455-3p can regulate PTEN and influence COL2A1 and MMP13. Apoptosis was detected by flow cytometry. A luciferase report was applied to verify the targeted binding. KO mice were applied to investigate PTEN and pAKT expression and the effect on chondrocytes in vivo. MiR-455-3p and PTEN were reverse in chondrogenesis and healthy cartilage versus OA cartilage. Similar trends were noted in IL-1β model. PTEN and MMP13 decreased and COL2A1 increased after overexpressing miR-455-3p, whereas the inhibition showed opposite results. Flow cytometry showed that miR-455-3p could reduce the apoptosis of chondrocytes. The results of luciferase revealed that miR-455-3p could affect fluorescence activity of PTEN by targeting its 3'-UTR. Finally, we found a marked increased in the expression of PTEN in KO mice relative to WT mice, while pAKT levels decreased. It can be supported that miR-455-3p can reduce the apoptosis of chondrocytes and alleviate OA through regulating PI3K/AKT pathway, which may be expected to be a target for the treatment of osteoarthritis.

Wen X ，Li H ，Sun H ，Zeng A ，Lin R ，Zhao J ，Zhang Z ... -  《-》

Circ_0116061 regulated the proliferation, apoptosis, and inflammation of osteoarthritis chondrocytes through regulating the miR-200b-3p/SMURF2 axis.

Zheng W ，Hou G ，Li Y 《Journal of Orthopaedic Surgery and Research》

MiR-128-3p Post-Transcriptionally Inhibits WISP1 to Suppress Apoptosis and Inflammation in Human Articular Chondrocytes via the PI3K/AKT/NF-κB Signaling Pathway.

Chen S ，Li B 《-》

Downregulation of miR-34a Promotes Proliferation and Inhibits Apoptosis of Rat Osteoarthritic Cartilage Cells by Activating PI3K/Akt Pathway.

To elucidate the expression and function of miR-34a in rat osteoarthritic cartilage cells, and further to explore its mechanism. Rat model of osteoarthritis was constructed and knee joint cartilage cells were isolated in vitro. Immunocytochemical staining was used for identification. qRT-PCR was used to detect the expression of miR-34a in cartilaginous tissues and cartilage cells. Cartilage cells were divided into blank control (BC), negative control (NC), miR-34a inhibitor (34aI), osteoarthritis model (OA), osteoarthritis model + negative control (OA + NC) and osteoarthritis model + miR-34a inhibitor (OA + 34aI) groups. Cell proliferation was detected by CCK-8 and colony formation assays. Cell apoptosis was studied by flow cytometry and Western blot. PI3K/AKT-pathway-related proteins were also analyzed by Western blot. To further validate the effect of miR-34a on the PI3K/Akt pathway, the cartilage cells were divided into blank control (BC), osteoarthritis model (OA), osteoarthritis model + miR-34a inhibitor (OA + 34aI), osteoarthritis model + PI3K activator (OA + IGF-1) and osteoarthritis model + miR-34a inhibitor + PI3K inhibitor (OA + 34aI + LY) groups, the experiments above were repeated. The expression of miR-34a in cartilaginous tissues and cells of osteoarthritis model was significantly higher than that in normal (p < 0.05). After silencing miR-34a gene, the cell proliferation and proteins expression of PI3K/Akt pathway were increased, while the apoptosis rate and expression of apoptosis-related proteins were decreased. Addition of PI3K activator also evidently promoted proliferation and inhibited apoptosis. The protein expression of Bax, Cleaved caspase-3 and Cleaved caspase-9 were dramatically decreased, while the ratios of p-PI3K/PI3K and p-Akt/Akt were increased in OA + IGF-1 group. Downregulation of miR-34a regulated proliferation and apoptosis of cartilage cells by activating PI3K/Akt pathway, providing a potential therapeutic approach for the treatment of osteoarthritis.

Tao H ，Cheng L ，Yang R 《Clinical Interventions in Aging》