Department of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
Department of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea; Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
Bone. 2019 Mar;120:432-438. doi: 10.1016/j.bone.2018.12.010. Epub 2018 Dec 14.
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.
Anoctamin 5（Ano5）突变负责颌骨发育不良，这是一种罕见的骨骼综合征。尽管 Ano5 与骨重塑密切相关，但 Ano5 在骨重塑中作用的分子机制仍不清楚。在这项研究中，我们研究了 Ano5 是否调节成骨细胞或破骨细胞分化以维持正常的骨重塑。下调 Ano5 的表达并不影响成骨细胞分化和矿化，而过表达 Ano5 则显著增强核因子 κB 受体激活剂配体（RANKL）诱导的破骨细胞分化。此外，Ano5 介导的 Akt 磷酸化导致激活的 T 细胞核因子 c1（NFATc1）的激活，表明 Ano5 通过激活 Akt-NFATc1 信号通路来调节破骨细胞分化。因此，我们的结果表明，Ano5 可能通过调节破骨细胞的功能而不是成骨细胞的功能参与骨重塑。
