Abstract
The increasing of intracellular calcium concentration is a fundamental process for mediating osteoclastogenesis, which is involved in osteoclastic bone resorption. Cytosolic calcium binds to calmodulin and subsequently activates calcineurin, leading to NFATc1 activation, a master transcription factor required for osteoclast differentiation. Targeting the various activation processes in osteoclastogenesis provides various therapeutic strategies for bone loss. Diverse compounds that modulate calcium signaling have been applied to regulate osteoclast differentiation and, subsequently, attenuate bone loss. Thus, in this review, we summarized the modulation of the NFATc1 pathway through various compounds that regulate calcium signaling and the calcium influx machinery. Furthermore, we addressed the involvement of transient receptor potential channels in osteoclastogenesis.
Highlights
Bone remodeling is balanced by the coordinated activities of osteoclastic resorption and osteoblastic formation [1]
macrophage colony-stimulating factor (M-CSF) is involved in the proliferation and survival of osteoclast precursors and RANKL induce osteoclast differentiation through binding to its receptor RANK and subsequent activation of nuclear factor of activated T cells (NFATc1), a master transcription factor required for osteoclast differentiation [8]
We focused on modulation of Ca2+ signaling through Ca2+ influx via transient receptor potential (TRP) channels and highlighted the diverse compounds, involved in the Ca2+ -mediated signaling pathway, in osteoclastogenesis
Summary
Bone remodeling is balanced by the coordinated activities of osteoclastic resorption and osteoblastic formation [1]. Cellular fusion is an essential element in osteoclast development that results in the formation of multinucleated giant cells responsible for bone resorption activity TRPV2 is expressed in RANKL-treated RAW264.7 cells and TRPV2-mediated spontaneous [Ca2+]i oscillations activate NFATc1 and promote osteoclast differentiation [30]. TRPV4-mediated Ca2+ influx and intracellular Ca2+ signaling activate NFATc1 and induce osteoclast differentiation and resorption activity [31,55]. Small interfering RNA (siRNA) knockdown of TRPV5 completely inhibits RANKL-induced Ca2+ influx at the late differentiation stage of osteoclasts in vitro and enhances bone resorption activity in human osteoclasts [20,62]. Estrogen inhibits osteoclast differentiation and bone resorption activity by increasing TRPV5 expression in postmenopausal osteoporosis [63].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
