High glucose inhibits receptor activator of nuclear factor‑κB ligand-induced osteoclast differentiation via downregulation of v‑ATPase V0 subunit d2 and dendritic cell‑specific transmembrane protein.

Abstract

The balance between bone formation and resorption is compromised in diabetes, which may contribute to the high risk of fractures in diabetic patients. However, the mechanism by which high glucose affects bone turnover remains to be elucidated. The present study demonstrated that high glucose inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. In order to examine the mechanism involved in the inhibition of osteoclastogenesis, the present study examined several key molecules involved in osteoclast differentiation, including v-ATPase V0 subunit d2 (Atp6V0d2), dendritic cell-specific transmembrane protein (DC-STAMP), c-fos and nuclear factor of activated T cells c1 (NFATc1). The expression levels of Atp6V0d2 and DC-STAMP are regulated by NFATc1 and c-fos, and are required for osteoclast fusion, which is important for osteoclast maturation. To the best of our knowledge, the present study demonstrated for the first time that high glucose decreased the gene expression of ATP6v0d2 and DC-STAMP in RAW264.7 cells mediated by RANKL. Therefore, the suppression of pre-osteoclast or osteoclast fusion may be essential for the inhibition of osteoclast differentiation.