Retinoic acid inhibits NFATc1 expression and osteoclast differentiation

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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

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NFATC Transcription Factors
Osteoclasts
Tretinoin
Osteogenesis
RANK Ligand
Vitamin A
Protein Isoforms
Cathepsin K
Retinoid X Receptors
Retinoic Acid Receptors
Bone Marrow Cells
Dendritic Cells
Monocytes
Transcription Factors
Up-Regulation
Eating
DNA
Genes
Proteins

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

Cite this

Retinoic acid inhibits NFATc1 expression and osteoclast differentiation. / Balkan, Wayne E; Rodríguez-Gonzalez, María; Pang, Manhui; Fernandez, Isabel; Troen, Bruce R.

In: Journal of Bone and Mineral Metabolism, Vol. 29, No. 6, 01.11.2011, p. 652-661.

Research output: Contribution to journalArticle

Balkan, Wayne E ; Rodríguez-Gonzalez, María ; Pang, Manhui ; Fernandez, Isabel ; Troen, Bruce R. / Retinoic acid inhibits NFATc1 expression and osteoclast differentiation. In: Journal of Bone and Mineral Metabolism. 2011 ; Vol. 29, No. 6. pp. 652-661.
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