Mechanical stimulation controls osteoclast function through the regulation of Ca2+-activated Cl− channel Anoctamin 1

Abstract

Mechanical force loading is essential for maintaining bone homeostasis, and unloading exposure can lead to bone loss. Osteoclasts are the only bone resorbing cells and play a crucial role in bone remodeling. The molecular mechanisms underlying mechanical stimulation-induced changes in osteoclast function remain to be fully elucidated. Our previous research found Ca2+-activated Cl− channel Anoctamin 1 (Ano1) was an essential regulator for osteoclast function. Here, we report that Ano1 mediates osteoclast responses to mechanical stimulation. In vitro, osteoclast activities are obviously affected by mechanical stress, which is accompanied by the changes of Ano1 levels, intracellular Cl− concentration and Ca2+ downstream signaling. Ano1 knockout or calcium binding mutants blunts the response of osteoclast to mechanical stimulation. In vivo, Ano1 knockout in osteoclast blunts loading induced osteoclast inhibition and unloading induced bone loss and. These results demonstrate that Ano1 plays an important role in mechanical stimulation induced osteoclast activity changes.

Daily low-intensity pulsed ultrasound stimulation mitigates joint degradation and pain in a post-traumatic osteoarthritis rat model

“…It has been reported that LIPUS stimulation increases prostaglandin E 2 (PGE 2 ) secretion from osteoblasts, which inhibits osteoclast formation [ 30 ]. More recently, a mechanosensitive calcium-activated chloride channel, anoctamin-1 (Ano1), was downregulated in response to mechanical stimulation in osteoclasts and inhibited their activity [ 31 ]. Taken together, it is likely that LIPUS may directly and indirectly inhibit osteoclasts through Ano1 and osteoblast PGE 2 production, respectively, that will be evaluated in future studies.…”