microRNA-148a-3p-targeting p300 protects against osteoblast differentiation and osteoporotic bone reconstruction

Aim: This study sets out to investigate the possible effects of miRNA-148a-3p (miR-148a-3p) on osteoblast differentiation and bone remodeling following osteoporosis. Materials & methods: Expression of miR-148a-3p, p300, Nrf2 and differentiation-related proteins (Runx2, Osteocalcin and Col1a1) was examined in the osteoblast MC3T3-E1 cell line, followed by identification of interaction between miR-148a-3p and p300 and between p300 and Nrf2. After ectopic expression and depletion experiments in MC3T3-E1 cells, cell proliferation, osteogenic mineralization and osteogenic differentiation were measured. Ovariectomy-induced osteoporosis mouse models were established to verify function of miR-148a-3p in vivo. Results: miR-148a-3p expression was restrained and p300 and Nrf2 expression was increased during osteoblast differentiation. miR-148a-3p inhibition or p300 upregulation enhanced proliferation and osteogenic differentiation in MC3T3-E1 cells. p300 was targeted by miR-148a-3p. Additionally, miR-148a-3p reduced BMD, bone volume relative to tissue volume ratio, trabecular bone, trabecular thickness and trabecular spacing in ovariectomy mice. Conclusion: Taken together, miR-148a-3p might prevent the osteoblast differentiation and bone remodeling by disrupting p300-dependent Nrf2 pathway activation.