Change search
ReferencesLink to record
Permanent link

Direct link
Retinoids inhibit differentiation of hematopoietic osteoclast progenitors
Umeå University, Faculty of Medicine, Department of Odontology, Oral Cell Biology.
Umeå University, Faculty of Medicine, Department of Odontology, Oral Cell Biology.
Umeå University, Faculty of Medicine, Department of Odontology, Oral Cell Biology.
Show others and affiliations
2009 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 23, no 10, 3526-3538 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Bethesda, Md.: Federation of American Societies for Experimental Biolog , 2009. Vol. 23, no 10, 3526-3538 p.
Keyword [en]
osteoporosis, c-Fos, NFAT2, ATRA
URN: urn:nbn:se:umu:diva-30072DOI: 10.1096/fj.09-132548PubMedID: 19546303OAI: diva2:279285
Available from: 2009-12-02 Created: 2009-12-02 Last updated: 2011-04-12Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Persson, EmmaHalén, MarieGranholm, SusanneSvensson, OllePettersson, UlrikaLie, AnitaLerner, Ulf H
By organisation
Oral Cell BiologyOrthopaedicsClinical Pharmacology
In the same journal
The FASEB Journal

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 130 hits
ReferencesLink to record
Permanent link

Direct link