Convergent signaling by acidosis and receptor activator of NF-kappaB ligand (RANKL) on the calcium/calcineurin/NFAT pathway in osteoclasts.

ABSTRACT: Systemic acidosis has detrimental effects on the skeleton, and local acidosis coincides with bone destruction in inflammatory and metastatic diseases. Acidification dramatically enhances osteoclastic resorption, although the underlying mechanism has remained elusive. We investigated the effect of acidosis on the osteoclastogenic transcription factor NFATc1, which upon dephosphorylation translocates from the cytoplasm to nuclei. Lowering extracellular pH dramatically increased accumulation of NFATc1 in nuclei of rat and rabbit osteoclasts to levels comparable with those induced by the proresorptive cytokine receptor activator of NF-kappaB ligand (RANKL). Activation of NFATc1 by RANKL was mediated by means of prolonged stimulation of the Ca2+/calmodulin-dependent protein phosphatase, calcine

SUBMITTER: Komarova SV 

PROVIDER: S-EPMC548977 | biostudies-literature | 2005 Feb

REPOSITORIES: biostudies-literature