Zoledronic Acid Regulates Osteoclasts via miR-483-5p in the BRONJ.

OBJECTIVES

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of bisphosphonate therapy, with unclear mechanisms. This study investigates the regulatory impact of zoledronic acid (ZOL) on osteoclasts and microRNA (miRNA) expression.

MATERIALS AND

METHODS

Raw264.7 cells and bone marrow-derived macrophages (BMMs) were used to assess ZOL's effects on proliferation and apoptosis. miRNA array analysis was performed during osteoclastogenesis with ZOL treatment. The role of miR-483-5p was examined using miR-mimics and miR-inhibitors. A rat BRONJ model was established for in vivo validation.

RESULTS

A concentration of 2 μM ZOL, which did not affect cell proliferation or apoptosis, was used in subsequent experiments. ZOL altered the expression of 64 miRNAs (39 upregulated, 25 downregulated). miR-483-5p mimics alleviated ZOL-induced inhibition of osteoclastogenesis, actin ring formation, bone resorption, and differentiation marker expression, whereas inhibitors enhanced these effects. In vivo, Ago-miR-483-5p promoted wound healing in the BRONJ model, while Antago-miR-483-5p impaired it.

CONCLUSIONS

ZOL modulates osteoclast function in BRONJ through miR-483-5p inhibition. miR-483-5p may serve as a novel therapeutic target for BRONJ treatment, providing new insights into managing this complication.