MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a.

BACKGROUND/AIMS: With the aging population increases, senile osteoporosis has become a global public health problem. Previous evidence has shown that miR-124 has important effects on the occurrence and development of osteoporosis. However, the role of miR-124 in the process of osteoclastogenesis is still obscure.

METHODS

First of all, we measured the expression level of miR-124 in bone marrow monocytes (BMMs) of osteoporotic mice (ovariectomized mice: OVX). Next, we evaluated the alteration of miR-124 during osteoclast differentiation of BMMs. Then, BMMs were transfected with miR-124 mimics or inhibitors to explore the influences of miR-124 on osteoclast differentiation of BMMs in vitro. Furthermore, bioinformatics analysis and luciferase reporter assay were performed for prediction and identification of the target of miR-124.

RESULTS

BMMs from OVX mice exhibited lower expression of miR-124 compared with Sham mice. Additionally, miR-124 was down-regulated when BMMs differentiated into osteoclasts. In addition, inhibition of miR-124 promoted BMMs differentiated into osteoclasts in vitro, whereas overexpression of miR-124 attenuated this procedure, demonstrated by increased expression of osteoclast specific genes and TRAP staining. Furthermore, Rab27a was confirmed to be the direct target of miR-124 by bioinformatics, Western blot and luciferase reporter assay analysis.

CONCLUSION

Our findings revealed that miR-124 has an important role in osteoclastogenesis via targeting Rab27a. Thus, targeting miR-124 promises a therapeutic potential in the treatment of osteoporosis.