AUTOREGULATION OF PERIODONTAL-LIGAMENT CELL PHENOTYPE AND FUNCTIONS BY TRANSFORMING GROWTH-FACTOR-BETA-1

During orthodontic tooth movement, mechanical forces acting on periodo ntal ligament (PDL) cells induce the synthesis of mediators which alte r the growth, differentiation, and secretory functions of cells of the PDL. Since the cells of the PDL represent a heterogeneous population, we examined mechanically stress-induced cytokine profiles in three se parate clones of human osteoblast-like PDL cells. Of the four pro-infl ammatory cytokines investigated, only IL-6 and TGF-beta 1 were up-regu lated in response to mechanical stress. However, the expression of oth er pro-inflammatory cytokines such as IL-1 beta, TNF-alpha, or IL-8 wa s not observed. To understand the consequences of the increase in TGF- beta 1 expression following mechanical stress, we examined the effect of TGF-beta 1 on PDL cell phenotype and functions. TGF-beta 1 was mito genic to PDL cells at concentrations between 0.4 and 10 ng/mL. Further more, TGF-beta 1 down-regulated the osteoblast-like phenotype of PDL c ells, i.e., alkaline phosphatase activity, calcium phosphate nodule fo rmation, expression of osteocalcin, and TGF-beta 1, in a dose-dependen t manner. Although initially TGF-beta 1 induced expression of type I c ollagen mRNA, prolonged exposure to TGF-beta 1 down-regulated the abil ity of PDL cells to express type I collagen mRNA. Our results further show that, within 4 hrs, exogenously applied TGF-beta 1 down-regulated IL-6 expression in a dose-dependent manner, and this inhibition was s ustained over a six-day period. In summary, the data suggest that mech anically stress-induced TGF-beta 1 expression may be a physiological m echanism to induce mitogenesis in PDL cells while down-regulating its osteoblast-like features and simultaneously reducing the IL-6-induced bone resorption.