Growth factors regulate expression of mineral associated genes in cementoblasts

Background: Knowledge of the responsiveness of cells within the periodontal region to specific bioactive agents is important for improving regenerativ e therapies. The aim of this study was to determine the effect of specific growth factors, insulin-like growth factor-I (IGF-I), platelet-derived grow th factor-BE (PDGF-BB), and transforming growth factor-beta (TGF-beta) on c ementoblasts in vitro and ex vivo. Methods: Osteocalcin (OC) promoter driven SV40 transgenic mice were used to obtain immortalized cementoblasts. Growth factor effects on DNA synthesis were assayed by [H-3]-thymidine incorporation. Northern analysis was used t o determine the effects of growth factors on gene expression profile. Effec ts of growth factors on cementoblast induced biomineralization were determi ned in vitro (von Kossa stain) and ex vivo (re-implantation of cells in imm unodeficient (SCID) mice). Results: All growth factors stimulated DNA synthesis compared to control. T wenty-four hour exposure of cells to PDGF-BB or TGF-beta resulted in a decr ease in bone sialoprotein (BSP) and osteocalcin (OCN) mRNAs while PDGF-BB a lso increased osteopontin (OPN) mRNA. Cells exposed to IGF-I for 24 hours e xhibited decreased transcripts for OCN and OPN with an upregulation of BSP mRNA noted at 72 hours. In vitro mineralization was inhibited by continuous application of PDGF-BB or TGF-beta, while cells exposed to these factors p rior to implantation into SCID mice still promoted biomineralization. Conclusions: These data indicate IGF-I, PDGF-BB, and TGF-beta influence mit ogenesis, phenotypic gene expression profile, and biomineralization potenti al of cementoblasts suggesting that such factors alone or in combination wi th other agents may provide trigger factors required for regenerating perio dontal tissues.