Role of anoctamin 5, a gene associated with gnathodiaphyseal dysplasia, in osteoblast and osteoclast differentiation.

Abstract

Anoctamin 5 (Ano5) mutations are responsible for gnathodiaphyseal dysplasia, a rare skeletal syndrome. Despite the close linkage of Ano5 to bone remodeling, the molecular mechanisms underlying the role of Ano5 in bone remodeling remain unknown. In this study, we investigated whether Ano5 regulates osteoblast or osteoclast differentiation to maintain normal bone remodeling. Downregulation of Ano5 expression did not affect osteoblast differentiation and mineralization, while ectopic expression of Ano5 significantly enhanced receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation. Furthermore, Ano5-mediated Akt phosphorylation resulted in nuclear factor of activated T-cells c1 (NFATc1) activation, indicating that Ano5 regulates osteoclast differentiation through activation of the Akt-NFATc1 signaling pathway. Thus, our results suggest a possibility that Ano5 is involved in bone remodeling through regulating the function of osteoclasts rather than that of osteoblasts.