Retinoids inhibit differentiation of hematopoietic osteoclast progenitors.

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.

Persson, EmmaUmeå universitet,Oral cellbiologi(Swepub:umu)empe0001 (författare)
Halén, MarieUmeå universitet,Oral cellbiologi (författare)
Granholm, SusanneUmeå universitet,Oral cellbiologi(Swepub:umu)suegrm99 (författare)
Svensson, OlleUmeå universitet,Ortopedi(Swepub:umu)olsv0001 (författare)
Pettersson, UlrikaUmeå universitet,Klinisk farmakologi(Swepub:umu)ulpe0007 (författare)
Lie, AnitaUmeå universitet,Oral cellbiologi(Swepub:umu)anli0007 (författare)
Lerner, Ulf HUmeå universitet,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine,Oral cellbiologi(Swepub:umu)ulle0001 (författare)
Umeå universitetOral cellbiologi (creator_code:org_t)

Ingår i:The FASEB journalBethesda, Md. : Wiley23:10, s. 3526-381530-68600892-6638

Av författaren/redakt...: Conaway, H Hersc ...; Persson, Emma; Halén, Marie; Granholm, Susann ...; Svensson, Olle; Pettersson, Ulri ...; visa fler...; Lie, Anita; Lerner, Ulf H; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Odontologi

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Ortopedi

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