MicroRNA‑22 contributes to dexamethasone‑induced osteoblast differentiation inhibition and dysfunction through targeting caveolin‑3 expression in osteoblastic cells

Abstract

Osteoporosis is a common complication of long-term use of glucocorticoids (GCs) characterized by the loss of bone mass and damage of the microarchitecture as well as osteoblast dysfunction. Previous studies have demonstrated that microRNA-22 (miR-22) is the negative modulator of osteogenesis that may target caveolin-3 (CAV3), which has been reported to enhance bone formation and inhibit the progression of osteoporosis as well as apoptosis. The present study aimed to investigate whether miR-22 may be involved in dexamethasone (DEX)-induced inhibition of osteoblast differentiation and dysfunction by regulating CAV3 expression. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure the expression of miR-22 and western blotting was performed to determine protein levels. The results demonstrated that miR-22 expression was upregulated in DEX-treated osteoblastic cells compared with the control group. In addition, miR-22 mimic aggravated, whereas miR-22 inhibitor mitigated DEX-induced damage in osteoblastic cells compared with the control groups. Additionally, CAV3 was identified as the target of miR-22 in osteoblasts using RT-qPCR, western blotting and dual-luciferase reporter gene assay analysis. The results also demonstrated that silencing of CAV3 blocked the beneficial effects of miR-22 inhibitor against DEX-induced cell damage and apoptosis in osteoblasts, as evidenced by the increased expression levels of cleaved caspase-3, Bax and alkaline phosphatase activity as well as decreased cell viability and Bcl-2 levels. Collectively, these results indicate a novel molecular mechanism by which miR-22 contributes to DEX-induced osteoblast dysfunction and apoptosis via the miR-22/CAV3 pathway.

Age- and Sex-Dependent Caveolar Gene Expression in Normoxic and Post-Ischemic Mouse Hearts

“…As Cav3 mRNA was consistantly down-regulated with aging in the male myocardium (to a lesser degree in females), we hypothesized whether this transcriptional repression could be related to microRNA regulation of gene expression as seen by others with cardiac aging and disease (Boon et al, 2013; Gatsiou et al, 2021; Bei et al, 2018). In-silico bioinformatic analysis of Cav3 and literature search (Chen et al, 2015; Li et al, 2021; Zhang et al, 2018) for Cav3 -related microRNAs revealed miR-22 & miR-101b as top candidates for regulation of Cav3 . Although miR-22 and miR-101b showed significant age-dependant changes in the normoxic heart, their expression pattern did not (inversely) correlate with Cav3 transcriptional changes seen in the normoxic and post-ischemic male hearts.…”