Mechanism of miR-15a regulating the growth and apoptosis of human knee joint chondrocytes by targeting SMAD2

Abstract

Objective: To investigate the effects of miR-15a on proliferation and apoptosis of human knee articular chondrocytes and explore its underlying mechanism. Methods: qRT-PCR was used to detect the expression of miR-15a in normal chondrocytes and knee arthritic chondrocytes; miR-con (transfected miR-con), miR-15a (transfected miR-15a mimics), anti-miRcon group (transfected anti-miR-con), anti-miR-15a group (transfected anti-miR-15a mimics), pcDNA group (transfected pcDNA), pcDNA-SMAD2 group (transfected pcDNA-SMAD2), the miR-15a þ pcDNA group (co-transfected miR-15a and pcDNA), miR-15a þ pcDNA-SMAD2 group (co-transfected miR-15a mimics and pcDNA-SMAD2), were transfected into knee articular chondrocytes by liposome method, respectively. The cell proliferation and apoptosis of each group were detected by MTT assay and flow cytometry. The protein expression of SMAD2 was detected by Western blot. The fluorescence activity of each group was detected by dual luciferase reporter gene assay. Results: The expression of miR-15a in knee arthritis chondrocytes was significantly increased (p < .05) compared with that in normal chondrocytes. Moreover, overexpression of miR-15a and silencing of SMAD2 inhibited proliferation and promoted apoptosis in knee arthritis chondrocyte. MiR-15a targeted SMAD2. Overexpression of SMAD2 reversed the inhibitory effects on proliferation and promotion effects on apoptosis induced by miR-15a in knee arthritis chondrocytes. Conclusion: miR-15a can inhibit the proliferation and promote apoptosis of knee arthritis chondrocytes. The mechanism may be related to SMAD2, which will provide a new target for the treatment of knee arthritis.

MiR-124-3p impedes the metastasis of non-small cell lung cancer via extracellular exosome transport and intracellular PI3K/AKT signaling

“…Recent research reported that the interaction between lncRNA and miRNA can modulate the expression of downstream genes and affect different biological functions [29][30][31][32]. To identify lncRNA that regulate miR-124-3p signaling, we used starBase v2.0 software to predict the lncRNA-miRNA interaction.…”

Knee Osteoarthritis Therapy: Recent Advances in Intra-Articular Drug Delivery Systems

“… [ 108 , 109 ] Lipofectamine TM 2000 kit miR-15a Targeting SMAD2 In vitro Human normal chondrocytes Inhibiting the proliferation and promoting apoptosis of knee arthritis chondrocytes. [ 110 ] Lipo2000 microRNA-143-3p Targeting BMPR2 In vitro BMSCs MiR-143-3p could regulate the differentiation process by targeting BMPR2 in BMSCs. [ 111 ] DSPE-PEG-maleimide/ HAP-1 peptide Prednisone / immunosuppressive peptide CP Targeting Synovial; Targeting Inflammation In vitro & vivo Synovial fibroblast like and endothelial cells; Rats Targeted liposomes specifically bound to rabbit FLS and human FLS and showed a 7–10 folds increase in vivo localization in affected joints compared to unaffected joints.…”

“…The targeting agents can be loaded into the liposomes. This strategy typically targets protein receptors or genes, such as CGS21680 (adenosine A2A receptor agonist), 108 , 109 miR-15a (a microRNA that silences SMAD2 gene expression), 110 and microRNA-143-3p (targeted regulation of BMPR2 expression). 111 The stable lipid bilayer structure of liposomes can help transport sensitive cargo into cells and enhance the effect of the agents.…”