Retinoic acid inhibits NFATc1 expression and osteoclast differentiation

Wayne Balkan, María Rodríguez-Gonzalez, Manhui Pang, Isabel Fernandez, Bruce R. Troen

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Ingestion of excess vitamin A appears to correlate with an increased fracture risk, an outcome that is likely mediated by retinoic acids (RAs); these are vitamin A metabolites that have dramatic effects on skeletal development. We studied the impacts of RA and isoform-specific RA receptor (RAR) agonists (α, β, and γ) on osteoclast formation (osteoclastogenesis) in two model systems: RAW264.7 cells and murine bone marrow-derived monocytes. The pan-RAR agonists, all-trans and 9-cis RA, inhibited receptor activator of nuclear factor kappa B ligand (RANKL)-mediated osteoclast differentiation in a concentration-dependent manner. Isoform-specific RAR agonists (α, β, and γ) also inhibited osteoclastogenesis, with the RARα agonist producing the most consistent reductions in both osteoclast number and size and total area covered. Inhibition of osteoclastogenesis correlated with reductions in expression, DNA binding, and nuclear abundance of nuclear factor of activated T cells c1 (NFATc1), a transcription factor critical for osteoclastogenesis. The upregulation of three NFATc1-responsive genes, cathepsin K, dendritic cell-specific transmembrane protein and osteoclast-associated receptor were similarly reduced following RA or RAR agonist exposure. These results suggest that RA blocks in vitro RANKL-mediated osteoclastogenesis by decreasing NFATc1 function.

Original languageEnglish (US)
Pages (from-to)652-661
Number of pages10
JournalJournal of Bone and Mineral Metabolism
Volume29
Issue number6
DOIs
StatePublished - Nov 1 2011

Keywords

  • Nuclear factor of activated T cells
  • Osteoclast
  • Retinoic acid
  • Retinoic acid receptor
  • Vitamin A

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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