TGF-βRI kinase activity mediates Emdogain-stimulated in vitro osteoclastogenesis.
OBJECTIVE
Emdogain, containing an extract of fetal porcine enamel matrix proteins, is a potent stimulator of in vitro osteoclastogenesis. The underlying molecular mechanisms are, however, unclear.


METHODS
Here, we have addressed the role of transforming growth factor-beta receptor type 1 (TGF-βRI) kinase activity on osteoclastogenesis in murine bone marrow cultures.


RESULTS
Inhibition of TGF-βRI kinase activity with SB431542 abolished the effect of Emdogain on osteoclastogenesis induced by receptor activator of nuclear factor kappa-B ligand or tumor necrosis factor-alpha. SB431542 also suppressed the Emdogain-mediated increase of OSCAR, a co-stimulatory protein, and dendritic cell-specific transmembrane protein and Atp6v0d2, the latter two being involved in cell fusion. Similar to transforming growth factor-beta1 (TGF-β), Emdogain could not compensate for the inhibition of IL-4 and IFNγ on osteoclast formation. When using the murine macrophage cell line RAW246.7, SB431542 and the smad-3 inhibitor SIS3 blocked Emdogain-stimulated expression of the transcription factor NFATc1.


CONCLUSIONS
Taken together, the data suggest that TGF-βRI kinase activity is necessary to mediate in vitro effects of Emdogain on osteoclastogenesis.


CONCLUSIONS
Based on these in vitro data, we can speculate that at least part of the clinical effects of Emdogain on osteoclastogenesis is mediated via TGF-β signaling.
Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland, reinhard.gruber@zmk.unibe.ch.
Reinhard
R
Gruber
Gilles
G
Roos
Jordi
J
Caballé-Serrano
Rick
R
Miron
Dieter D
DD
Bosshardt
Anton
A
Sculean
D000818:Animals; D002478:Cells, Cultured; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*
D003746:Dental Enamel Proteins; D018125:Receptors, Transforming Growth Factor beta; C109069:enamel matrix proteins; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I