MicroRNA‑142 protects MC3T3‑E1 cells against high glucose‑induced apoptosis by targeting β‑catenin

Abstract

Osteoporosis, characterized by decreased mineral density and bone mass, is triggered by various detrimental factors and often causes further complications, including fractures. Aberrant expression of microRNAs (miRs) has been associated with the pathogenesis of osteoporosis. Recently, miR-142 was reported to be downregulated in osteoblasts; however, the underlying mechanism of miR-142 in mediating the development of osteoporosis remains unclear. In the present study, high glucose induced the downregulation of miR-142 mRNA expression and promoted the apoptosis of MC3T3-E1 cells. miR-142-mimics significantly protected against high glucose-induced apoptosis, upregulated the expression levels of B-cell lymphoma 2 (Bcl-2) and downregulated the protein expression levels of β-catenin, Bcl-2 associated X (Bax) and caspase-3. Furthermore, β-catenin was identified as a direct target of miR-142 using luciferase reporter assays. Similar to the effects of miR-142 inhibitors, overexpression of β-catenin aggravated the apoptosis of MC3T3-E1 cells, as demonstrated by the upregulation of Bax and caspase-3, and the downregulation of Bcl-2 expression levels. In conclusion, miR-142 protects MC3T3-E1 cells against high glucose-induced apoptosis by targeting β-catenin.

7-Ketocholesterol Induces Oxiapoptophagy and Inhibits Osteogenic Differentiation in MC3T3-E1 Cells

“…MC3T3-E1 cells were purchased and cultured as in a previous study [ 7 ]. Briefly, cells were cultured in α-MEM under standard conditions.…”

“…The pathogenesis and progression of OP might be affected by aging, genetic factors, bad living habits, and nutritional deficiency, among which, the imbalance of bone homeostasis is one of the key factors [ 3 , 4 ]. There is increasing evidence that lipid metabolism disorders, such as atherosclerosis (AS) and OP, share common underlying pathogenesis involving bone and vascular mineralization, as well as age-related degenerative processes [ 5 , 6 , 7 ]. However, the specific mechanism of action between lipid and bone metabolism disorders remains unclear.…”

Functional micro-RNA drugs acting as a fate manipulator in the regulation of osteoblastic death

“…72 Controversially, Zheng et al reported that miR-142 has a protective effect on osteoblasts in a high-glucose environment. 73 They showed that miR-142 can block the Wnt signaling pathway by targeting β-catenin to suppress the onset of high glucose-induced apoptosis. Another debated one is miR-146a, which was reported to be engaged in both promoting and inhibiting osteoblastic apoptosis.…”

The miRNA‐144‐5p/IRS1/AKT axis regulates the migration, proliferation, and mineralization of osteoblasts: A mechanism of bone repair in diabetic osteoporosis

“…Recently, there has been growing interest in exploring the function of miRNAs in HG‐induced osteoblasts (B. Liu et al, 2012). For example, miRNA‐142 can protect MC3T3‐E1 cells against HG‐induced apoptosis by targeting β‐catenin (Zheng et al, 2020), miRNA‐590‐5p can antagonize the inhibitory effect of HG by suppressing Smad7 (Chen et al, 2019). Emerging evidence suggested that miRNA‐144 participates in osteoblasts' differentiation and proliferation.…”