miR-142-5p promotes the osteoclast differentiation of bone marrow-derived macrophages via PTEN/PI3K/AKT/FoxO1 pathway.

ABSTRACT

It is increasingly recognized that microRNAs (miRNAs) are a kind of important regulators, which are involved in the pathogenesis and development of various human diseases. However, the underlying effects and mechanism of miR-142-5p on the osteoclast differentiation of bone marrow-derived macrophages (BMMs) have not been elucidated. The aim of the present study is to explore the molecular mechanisms that regulate the osteoclastogenesis of BMMs for providing more efficient methods for treating bone-related diseases. In the present study, BMMs were isolated from rats and cultured. Moreover, receptor activators of NF-kB ligands were used to induce the osteoclast differentiation of BMMs. Furthermore, we analyzed the effects of miR-142-5p mimics/inhibitor on the osteoclastogenesis of BMMs. The results indicated that the downregulation of miR-142-5p inhibited the osteoclastogenesis of BMMs, whereas the overexpression enhanced this process. PTEN was testified to be a direct target of miR-142-5p, and its effects on the osteoclastogenesis were also described. Most importantly, treatment of LY29004 (an inhibitor of the PI3k/Akt pathway) can attenuate miR-142-5p osteoclastogenesis effects, while the inhibition effects of LY29004 on the osteoclastogenesis were abolished by knockdown of FoxO1. Taken together, our findings demonstrated that miR-142-5p promotes the osteoclastogenesis of BMMs through PI3k/Akt/FoxO1 pathway via targeting PTEN.