Autoregulation of Periodontal Ligament Cell Phenotype and Functions by Transforming Growth Factor-β1

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Abstract
During orthodontic tooth movement, mechanical forces acting on periodontal ligament (PDL) cells induce the synthesis of mediators which alter 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 separate clones of human osteoblast-like PDL cells. Of the four pro-inflammatory cytokines investigated, only IL-6 and TGF-β1 were up-regulated in response to mechanical stress. However, the expression of other pro-inflammatory cytokines such as IL-1β, TNF-a, or IL-8 was not observed. To understand the consequences of the increase in TGF-β1 expression following mechanical stress, we examined the effect of TGF-β1 on PDL cell phenotype and functions. TGF-β1 was mitogenic to PDL cells at concentrations between 0.4 and 10 ng/mL. Furthermore, TGF-β1 down-regulated the osteoblast-like phenotype of PDL cells, i.e., alkaline phosphatase activity, calcium phosphate nodule formation, expression of osteocalcin, and TGF-β1, in a dose-dependent manner. Although initially TGF-β1 induced expression of type I collagen mRNA, prolonged exposure to TGF-β1 down-regulated the ability of PDL cells to express type I collagen mRNA. Our results further show that, within 4 hrs, exogenously applied TGF-β1 down-regulated IL-6 expression in a dose-dependent manner, and this inhibition was sustained over a six-day period. In summary, the data suggest that mechanically stress-induced TGF-pl expression may be a physiological mechanism to induce mitogenesis in PDL cells while down-regulating its osteoblast-like features and simultaneously reducing the IL-6-induced bone resorption.

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