The activin-binding protein follistatin is expressed in developing murine molar and induces odontoblast-like cell differentiation in vitro.
It has recently been shown that mice deficient in activin-beta A subunits and follistatin exhibit major defects in dentition. To increase understanding of the roles played by these molecules during tooth development, we determined the temporospatial expression of activin-beta A subunit and follistatin messenger RNA and their corresponding proteins in developing murine molars (between day E 14 and 2 days after birth). The effects of recombinant human activin A and its binding protein follistatin on odontoblast differentiation were also studied in cultures of dental papillae (DP) isolated from the mandibular first molars of E-17-day mice. In situ hybridization indicated that transcripts for activin-beta A subunit were abundant in pre-odontoblasts at the tips of forming cusps prior to odontoblast terminal differentiation, and transcripts for follistatin in overlying inner enamel epithelial cells (pre-ameloblasts). Pre-odontoblasts were also weakly immunoreactive in relation to activin-beta A subunit, pre-ameloblasts in relation to follistatin. When follistatin was added at different concentrations to a DP culture model (2-14 nmol/DP) together with heparin at constant concentration, differentiation of odontoblast-like cells was induced, as evidenced by polarization and deposition of extracellular matrix in vitro, to extents depending on the follistatin concentration. In contrast, the addition of activin A (2 nmol/DP) had no effect on the differentiation parameters studied. These findings suggest that the activin-follistatin system regulates odontoblast differentiation during tooth development. In particular, we suggest that binding of endogenous activin A by follistatin may allow odontoblast terminal differentiation to occur.
Heikinheimo
K
K
Institut de Biologie Médicale, Université Louis Pasteur, Faculté de Médecine, INSERM U 424, Strasbourg, France.
Bègue-Kirn
C
C
Ritvos
O
O
Tuuri
T
T
Ruch
J V
JV
D028341:Activins; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D038681:Follistatin; D006023:Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007265:Inhibins / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008963:Molar / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D009804:Odontoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D038681:Follistatin; D006023:Glycoproteins; D006133:Growth Substances; D012333:RNA, Messenger; D011994:Recombinant Proteins; D028341:Activins; D007265:Inhibins; D006493:Heparin