Growth factors regulate expression of mineral associated genes in cementoblasts.

Restoring lost periodontium, the ultimate goal of regenerative periodontal therapy, requires functional and anatomical reconstruction of a multitude of tissues including cementum, periodontal ligament, bone, and gingiva. Toward this goal research efforts have focused on determining the cells, factors, and mechanisms fostering periodontal wound healing. Increased understanding of mediators required for promoting periodontal regeneration has led to improved techniques directed toward enhancing healing and regeneration of periodontal tissues lost as a consequence of disease.1-3 A specific concern for the clinician has been the limited predictability of forming regenerative cementum, which is considered a prerequisite for complete restoration of periodontal tissues.4 Therefore, understanding the molecular mechanisms and cell dynamics of cementogenesis during development and healing of periodontal tissues is important to improving regenerative techniques. The molecular and cellular events involved in controlling cementogenesis have not been studied widely due to limited tools, including lack of cementoblast cultures.5,6 Toward this aim our laboratory determined the timed and spatial expression of molecules during tooth root development in situ.7-9 Root lining cells, cementoblasts, were found to express markers associated with cells involved in mineral formation such as bone sialoprotein (BSP) and osteocalcin (OCN). This selective expression profile enabled us to establish cementoblast cell lines independent from surrounding periodontal ligament (PDL) cells. The availability of cementoblast cell lines allows us to seek answers to many questions that previously have been difficult to address. The accumulating evidence indicating that growth factors, under appropriate conditions, have positive effects on wound healing10,11 prompted us to evaluate their effects on cementoblasts in vitro. Growth factors possess diverse activities including the ability to stimulate cell migration, proliferation, differentiation, and matrix synthesis, all activities known to be important in tissue repair.12 More specifically, increasing evidence has accumulated from both in vitro13-16 and in vivo17-21 studies to support a role for growth factors for use in regenerative periodontal therapy. Factors considered to have a positive impact on periodontal regeneration include platelet-derived growth factor (PDGF); insulin-like growth factor (IGF); fibroblast growth factor (FGF); transforming growth factor-β 1, -2, and -3, (TGF-β); and bone morphogenetic proteins (BMPs) belonging to TGF-β superfamily.3,22 However, specific cells, as well as the response of cells to these factors, have not been completely defined.4,10 Most notably, limited data exist regarding the effects of growth factors on cementoblasts. Knowledge as to the responsiveness of cementoblasts to growth factors may provide critical information important for designing regenerative therapies. The aim of this investigation was to determine whether the growth factors IGF-I, PDGF-BB, and TGF-β, known to have an effect on PDL cells and on osteoblasts, alter cementoblast behavior. Cell activities examined included mitogenic activity in vitro, cell differentiation in vitro, and induction of mineralization in vitro and ex vivo.