Anoctamin 1 controls bone resorption by coupling Cl^- channel activation with RANKL-RANK signaling transduction.

ABSTRACT: Osteoclast over-activation leads to bone loss and chloride homeostasis is fundamental importance for osteoclast function. The calcium-activated chloride channel Anoctamin 1 (also known as TMEM16A) is an important chloride channel involved in many physiological processes. However, its role in osteoclast remains unresolved. Here, we identified the existence of Anoctamin 1 in osteoclast and show that its expression positively correlates with osteoclast activity. Osteoclast-specific Anoctamin 1 knockout mice exhibit increased bone mass and decreased bone resorption. Mechanistically, Anoctamin 1 deletion increases intracellular Cl^- concentration, decreases H⁺ secretion and reduces bone resorption. Notably, Anoctamin 1 physically interacts with RANK and this interaction is

SUBMITTER: Sun W 

PROVIDER: S-EPMC9130328 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature