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Retinoids inhibit differentiation of hematopoetic osteoclast progenitors
Author(s) -
Conaway H. Herschel,
Persson Emma,
Halen Marie,
Granholm Susanne,
Svensson Olle,
Pettersson Ulrika,
Lie Anita,
Lerner Ulf H.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-132548
Subject(s) - osteoclast , progenitor cell , microbiology and biotechnology , progenitor , biology , stem cell , medicine , receptor
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‐irans‐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 RARα, with no involvement of PPARβ/δ. The results suggest that activation of RARα by retinoids in myeloid hematopoietic precursor cells decreases osteoclast formation by altering expression of the transcription factors c‐Fos, NFAT2, and MafB.—Conaway, H. H., Persson, E., Halen, M., Granholm, S., Svensson, O., Pettersson, U., Lie, A., Lerner, U. H. Retinoids inhibit differentiation of hematopoetic osteoclast progenitors. FASEB J . 23, 3526–3538 (2009). www.fasebj.org