Role of anoctamin 5, a gene associated with gnathodiaphyseal dysplasia, in osteoblast and osteoclast differentiation.
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.
['Kim|Jung Ha|JH|', 'Kim|Kabsun|K|', 'Kim|Inyoung|I|', 'Seong|Semun|S|', 'Kim|Sang Wan|SW|', 'Kim|Nacksung|N|']
D000818:Animals D000831:Animals, Newborn D000075368:Anoctamins D002454:Cell Differentiation D005786:Gene Expression Regulation D020022:Genetic Predisposition to Disease D006801:Humans D051379:Mice D050778:NFATC Transcription Factors D010006:Osteoblasts D010010:Osteoclasts D010012:Osteogenesis D010013:Osteogenesis Imperfecta D010766:Phosphorylation D051057:Proto-Oncogene Proteins c-akt D015398:Signal Transduction
Anoctamin 5 Gnathodiaphyseal dysplasia Osteoblast Osteoclast