title: FGF-2 potently induces both proliferation and DSP expression in collagen type I gel cultures of adult incisor immature pulp cells.
abstract: We investigated the effects of both cytokines and extracellular matrices on the proliferation and differentiation of immature adult rat incisor dental pulp cells. These immature cells, which have a high-proliferative potency in vitro and do not express mRNAs for dentin non-collagenous proteins such as dentin sialoprotein (DSP), bone sialoprotein (BSP), and osteocalcin, exist in the root regions of adult rat incisors. Fibroblast growth factor-2 (FGF-2) stimulated the proliferation of these immature cells and the subsequent production of mineralized calcium was induced by beta-glycerophosphate treatment. Additionally, FGF-2 dramatically induced the expression of DSP and BSP mRNAs, but only in collagen type I gel cultures, whereas neither plate-coated collagen type I nor fibronectin, laminin or collagen type IV cultures could produce this effect and generate sufficient physiological levels of these transcripts. Although bone morphogenetic protein-4 could not induce the proliferation of immature dental pulp cells nor upregulate DSP mRNA expression, it had a synergistic effect upon DSP transcript levels in conjunction with FGF-2. These results suggest that both the presence of FGF-2 and the three-dimensional formation of immature dental pulp cells in collagen type I gel cultures are essential for both DSP expression and odontoblast differentiation. These observations provide valuable information concerning the study of the commitment and differentiation of odontoblast lineages, and also provide a basis for the rational design of cytokine and extracellular matrix based compounds for regenerative therapies in new dental treatments.
authors.affiliation: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Yamazaki 2641, Noda, Chiba 278-8510, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Nakao
authors.forename: Makoto
authors.initials: M
authors.lastname: Itoh
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tomita
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tomooka
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005782:Gels / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007180:Incisor / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D058574:Integrin-Binding Sialoprotein; D010750:Phosphoproteins; D011498:Protein Precursors / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012795:Sialoglycoproteins / Q000096:biosynthesis; D014018:Tissue Distribution; D023822:Tissue Engineering / Q000379:methods; D000099311:Dentin Sialophosphoprotein
chemical_list: D024042:Collagen Type I; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D016222:Fibroblast Growth Factor 2; D005782:Gels; D058574:Integrin-Binding Sialoprotein; D010750:Phosphoproteins; D011498:Protein Precursors; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C546873:Ibsp protein, rat