The function of miR-218 and miR-618 in postmenopausal osteoporosis

OBJECTIVE: Postmenopausal osteoporosis (POMP) is a serious disorder with significant physical, psychosocial, and financial consequences, which greatly reduce the postmenopausal women’s life quality. The related issues of postmenopausal osteoporosis are increasingly concerned by society. Past researches have shown that miRNAs play an important role in the occurrence and development of postmenopausal osteoporosis. However, the role of miR-218 and miR-618 in the osteoporosis regulation is still unclear.

MATERIALS AND METHODS: First of all, we investigated the alteration of miR-218 and miR-618 during osteoclastogenesis of RAW264.7 cells. Next, we transfected RAW264.7 cells with miR-218 or miR-618 mimics and inhibitors to explore the influences of miR-218 and miR-618 on osteoclast differentiation. Then, we conducted bioinformatics analysis and luciferase reporter assay to identify and test the target gene of miR-218 and miR-618.

RESULTS: MiR-218 and miR-618 were down-regulated when RAW264.7 cells differentiated into osteoclasts. In addition, overexpression of miR-218 or miR-618 attenuated RAW264.7 cells differentiated into osteoclasts in vitro, whereas inhibition of miR-218 or miR-618 promoted this progress. This was demonstrated by increased expression of osteoclast-specific genes and TRAP staining. TLR-4 was confirmed to be the direct target of miR-218 and miR-618 by bioinformatics and luciferase reporter assay.

CONCLUSIONS: These results suggested that miR-218 and miR-618 play an important role in osteoclastogenesis via TLR-4/MyD88/NF-κB signaling pathway. Thus, targeting miR-218 and miR-618 promise a therapeutic potential in the treatment of osteoporosis.

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