TGF-βRI kinase activity mediates Emdogain-stimulated in vitro osteoclastogenesis.

Gruber, Reinhard; Roos, Gilles; Caballé Serrano, Jordi; Miron, Rick; Bosshardt, Dieter; Sculean, Anton (2014). TGF-βRI kinase activity mediates Emdogain-stimulated in vitro osteoclastogenesis. Clinical oral investigations, 18(6), pp. 1639-1646. Springer 10.1007/s00784-013-1129-6

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OBJECTIVES 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. MATERIAL AND 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. CLINICAL RELEVANCE 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > School of Dental Medicine > Department of Periodontology

UniBE Contributor:

Gruber, Reinhard; Caballé Serrano, Jordi; Bosshardt, Dieter and Sculean, Anton

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1432-6981

Publisher:

Springer

Language:

English

Submitter:

Eveline Carmen Schuler

Date Deposited:

08 Jan 2015 12:18

Last Modified:

25 Jan 2017 12:15

Publisher DOI:

10.1007/s00784-013-1129-6

PubMed ID:

24221580

BORIS DOI:

10.7892/boris.61498

URI:

https://boris.unibe.ch/id/eprint/61498

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