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

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Abstract

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.

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Acknowledgments

We thank Catherine Solioz for her skillful technique assistance. This work was supported in part by the Straumann Institute.

Conflict of interest

The authors declare to have no conflict of interest related to this study.

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Authors and Affiliations

  1. Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland

    Reinhard Gruber, Rick Miron, Dieter D. Bosshardt & Anton Sculean

  2. Department of Oral Surgery and Stomatology, School of Dental Medicine, University of Bern, Bern, Switzerland

    Reinhard Gruber, Jordi Caballé-Serrano & Dieter D. Bosshardt

  3. Laboratory of Oral Cell Biology, School of Dental Medicine, University of Bern, Freiburgstrasse 7, 3010, Bern, Switzerland

    Reinhard Gruber, Gilles Roos & Jordi Caballé-Serrano

  4. Robert K. Schenk Laboratory of Oral Histology, School of Dental Medicine, University of Bern, Bern, Switzerland

    Dieter D. Bosshardt

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  1. Reinhard Gruber
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Correspondence to Reinhard Gruber.

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Gruber, R., Roos, G., Caballé-Serrano, J. et al. TGF-βRI kinase activity mediates Emdogain-stimulated in vitro osteoclastogenesis. Clin Oral Invest 18, 1639–1646 (2014). https://doi.org/10.1007/s00784-013-1129-6

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  • DOI: https://doi.org/10.1007/s00784-013-1129-6

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