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- Title
Retinoic acid inhibits NFATc1 expression and osteoclast differentiation.
- Authors
Balkan, Wayne; Rodríguez-Gonzalez, María; Pang, Manhui; Fernandez, Isabel; Troen, Bruce; Rodríguez-Gonzalez, María; Troen, Bruce R
- 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.
- Subjects
TRETINOIN; VITAMIN A; OSTEOCLASTS; BONE cells; T cells; NF-kappa B; ACID phosphatase; ANIMAL experimentation; BIOLOGICAL models; BONE growth; CELL differentiation; CELL lines; CELL receptors; COMPARATIVE studies; ELECTROPHORESIS; HETEROCYCLIC compounds; ISOENZYMES; MACROPHAGES; RESEARCH methodology; MEDICAL cooperation; MEMBRANE proteins; MICE; POLYMERASE chain reaction; PROTEINS; PROTEOLYTIC enzymes; RESEARCH; WESTERN immunoblotting; BIOINFORMATICS; EVALUATION research; REVERSE transcriptase polymerase chain reaction; PHARMACODYNAMICS
- Publication
Journal of Bone & Mineral Metabolism, 2011, Vol 29, Issue 6, p652
- ISSN
0914-8779
- Publication type
journal article
- DOI
10.1007/s00774-011-0261-0