PMID- 19546303
OWN - NLM
STAT- MEDLINE
DCOM- 20091105
LR  - 20220321
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 23
IP  - 10
DP  - 2009 Oct
TI  - Retinoids inhibit differentiation of hematopoietic osteoclast progenitors.
PG  - 3526-38
LID - 10.1096/fj.09-132548 [doi]
AB  - Whether vitamin A promotes skeletal fragility, has no effect on fracture rate, or 
      protects against bone loss is unclear. In the present study, effects of retinoids 
      on osteoclast differentiation in cultured mouse bone marrow cells (BMCs), bone 
      marrow macrophages (BMMs), spleen cells, and RAW264.7 cells were evaluated by 
      analyzing osteoclast formation and expression of genes important in signal 
      transduction and osteoclast function. All-trans-retinoic acid (ATRA) did not 
      stimulate osteoclastogenesis in BMCs, but inhibited hormone and RANKL-induced 
      gene expression and formation of osteoclasts. In BMMs, spleen cells, and RAW264.7 
      cells, osteoclast differentiation and formation stimulated by M-CSF/RANKL were 
      inhibited (IC(50) = 0.3 nM) by ATRA. The effect was exerted at an early step of 
      RANKL-induced differentiation. ATRA also abolished increases of the transcription 
      factors c-Fos and NFAT2 stimulated by RANKL and suppressed down-regulation of the 
      antiosteoclastogenic transcription factor MafB. By comparing effects of several 
      compounds structurally related to ATRA, as well as by using receptor antagonists, 
      evaluation pointed to inhibition being mediated by RARalpha, with no involvement 
      of PPARbeta/delta. The results suggest that activation of RARalpha by retinoids 
      in myeloid hematopoietic precursor cells decreases osteoclast formation by 
      altering expression of the transcription factors c-Fos, NFAT2, and MafB.
FAU - Conaway, H Herschel
AU  - Conaway HH
AD  - Department of Physiology and Biophysics, University of Arkansas for Medical 
      Sciences, Little Rock, Arkansas, USA.
FAU - Persson, Emma
AU  - Persson E
FAU - Halen, Marie
AU  - Halen M
FAU - Granholm, Susanne
AU  - Granholm S
FAU - Svensson, Olle
AU  - Svensson O
FAU - Pettersson, Ulrika
AU  - Pettersson U
FAU - Lie, Anita
AU  - Lie A
FAU - Lerner, Ulf H
AU  - Lerner UH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090622
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (RANK Ligand)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Hematopoiesis/*drug effects
MH  - Macrophages/cytology/drug effects/physiology
MH  - Mice
MH  - Myeloid Progenitor Cells/cytology/*drug effects/physiology
MH  - Osteoclasts/*cytology
MH  - RANK Ligand/metabolism
MH  - Receptors, Retinoic Acid/agonists/metabolism
MH  - Signal Transduction/drug effects
MH  - Tretinoin/*pharmacology
EDAT- 2009/06/24 09:00
MHDA- 2009/11/06 06:00
CRDT- 2009/06/24 09:00
PHST- 2009/06/24 09:00 [entrez]
PHST- 2009/06/24 09:00 [pubmed]
PHST- 2009/11/06 06:00 [medline]
AID - fj.09-132548 [pii]
AID - 10.1096/fj.09-132548 [doi]
PST - ppublish
SO  - FASEB J. 2009 Oct;23(10):3526-38. doi: 10.1096/fj.09-132548. Epub 2009 Jun 22.