Enamel matrix derivative inhibits adipocyte differentiation of 3T3-L1 cells via activation of TGF-βRI kinase activity.
Enamel matrix derivative (EMD), an extract of fetal porcine enamel, and TGF-β can both suppress adipogenic differentiation. However, there have been no studies that functionally link the role of EMD and TGF-β in vitro. Herein, we examined whether TGF-β signaling contributes to EMD-induced suppression of adipogenic differentiation. Adipogenesis was studied with 3T3-L1 preadipocytes in the presence of SB431542, an inhibitor of TGF-βRI kinase activity. SB431542 reversed the inhibitory effect of EMD on adipogenic differentiation, based on Oil Red O staining and mRNA expression of lipid regulated genes. SB431542 also reduced EMD-stimulated expression of connective tissue growth factor (CTGF), an autocrine inhibitor of adipogenic differentiation. Moreover, short interfering (si)RNAs for CTGF partially reversed the EMD-induced suppression of lipid regulated genes. We conclude that the TGF-βRI - CTGF axis is involved in the anti-adipogenic effects of EMD in vitro.
Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland. reinhard.gruber@zmk.unibe.ch
Reinhard
R
Gruber
Dieter D
DD
Bosshardt
Richard J
RJ
Miron
Anja C
AC
Gemperli
Daniel
D
Buser
Anton
A
Sculean
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006358:Hot Temperature; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D003746:Dental Enamel Proteins; D004149:Dioxoles; D018125:Receptors, Transforming Growth Factor beta; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; C109069:enamel matrix proteins; D000077154:Rosiglitazone; D055513:Connective Tissue Growth Factor; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D007213:Indomethacin