The Role of Ca2+-NFATc1 Signaling and Its Modulation on Osteoclastogenesis

Int J Mol Sci. 2020 May 21;21(10):3646. doi: 10.3390/ijms21103646.

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.

Keywords: NFAT; calcium signaling; osteoclast; transient receptor potential channels.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium Signaling*
  • Humans
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism*
  • Osteoclasts / cytology
  • Osteoclasts / metabolism*
  • Osteogenesis*
  • Transient Receptor Potential Channels / genetics
  • Transient Receptor Potential Channels / metabolism

Substances

  • NFATC Transcription Factors
  • Transient Receptor Potential Channels