OIP5-AS1/miR-335-5p regulates osteoblast proliferation and injury in glucocorticoid-induced osteoporosis in male mice

Clinical use of glucocorticoids in large quantities over a long period of time causes glucocorticoid-induced osteoporosis (GIOP). lncRNA OIP5-AS1 has elevated levels in delayed fracture healing, so the present study explored the role of OIP5-AS1 in a model of GIOP. The GIOP model was induced in mice by different doses of dexamethasone. The levels of OIP5-AS1, miR-335-5p, LC3-II, P62 mRNA, and four markers of osteogenic differentiation were assessed by RT-qPCR in the serum of GIOP mice and MC3T3-E1 cells. Cell proliferation was assessed by the CCK-8 kit. Lactic acid (LA) was assayed by a LA kit. The binding sites of OIP5-AS1 and miR-335-5p were predicted by the ENCORI database. DLR assay verified the binding relationship between OIP5-AS1 and miR-335-5p. GIOP mice had elevated levels of OIP5-AS1 expression, elevated lactate levels, increased oxidative stress, active autophagy, and reduced levels of osteogenic differentiation. After knocking down OIP5-AS1 in cellular models, miR-335-5p levels were elevated, lactate levels were decreased, oxidative stress levels were decreased, autophagy was inhibited, and osteogenic differentiation was increased. However, after transfection of miR-335-5p inhibitor, the cells had elevated lactate levels, decreased proliferative capacity, increased oxidative levels, active autophagic behavior, and decreased osteogenic differentiation. OIP5-AS1 levels were elevated in the GIOP model. Knockdown of OIP5-AS1 resulted in elevated miR-335-5p levels, enhanced proliferation and differentiation of osteoblasts, and suppression of autophagy and oxidative stress. Therefore, OIP5-AS1 may alleviate the development of GIOP through miR-335-5p.