Overexpression of miRNA-22-3p attenuates osteoporosis by targeting MAPK14

Osteoporosis (OP) results from an imbalance between bone formation, which is regulated by osteoblasts, and bone resorption, which is mediated by osteoclasts. MicroRNA-22-3p (miR-22-3p) expression is decreased during the process of osteoclast differentiation and p38α mitogen-activated protein kinase (MAPK)14 promotes the proliferation and differentiation of osteoclast progenitors. However, whether miR-22-3p could target MAPK14 to regulate the progression of OP remains unknown, which was the aim of the present study. CD14⁺ PBMCs were used for the establishment of osteoclastic differentiation in vitro. In the present study, reverse transcription quantitative PCR was used to determine the mRNA expression of MAPK14, tartrate resistant acid phosphatase (TRAP), nuclear factor of activated T-cells (NFATC1) and cathepsin K (CTSK). Western blotting was applied to determine the protein expression of MAPK14, TRAP, NFATC1, CTSK, p-p65 and p65. Dual luciferase reporter assay was applied to confirm the relation between miR-22-3p and MAPK14. Cell Counting Kit-8 assay and flow cytometry assays were used to determine the cell proliferation and cell apoptosis, respectively. The results demonstrated that miR-22-3p expression was lower while MAPK14 expression was higher in the serum from patients with OP compared with healthy volunteers. Furthermore, miR-22-3p expression was negatively correlated with MAPK14 expression in patients with OP. In addition, miR-22-3p expression was decreased and MAPK14 expression was increased during the progression of CD14⁺peripheral blood mononuclear cells (PBMCs) osteoclastic differentiation in a time-dependent manner. Furthermore, miR-22-3p inhibited the proliferation and differentiation and promoted the apoptosis of CD14⁺PBMCs by targeting MAPK14. In summary, the findings from the present study suggested that miR-22-3p may serve a potential therapeutic role in patients with OP.