Effects of TGF-ß1 on the proliferation and differentiation of human periodontal ligament cells and a human periodontal ligament stem/progenitor cell line.

ABSTRACT

Periodontal ligament (PDL) is a specialized connective tissue that influences the lifespan of the tooth. Transforming growth factor-ß1 (TGF-ß1) is a multifunctional cytokine, but little is known about the effects of TGF-ß1 on PDL cells. Our aim has been to demonstrate the expression of TGF-ß1 in rat PDL tissues and to evaluate its effects on the proliferation and gene expression in human PDL cells (HPLCs) and a human PDL stem/progenitor cell line, line 1-11, that we have recently developed. The expression of TGF-ß1 in the entire PDL tissue was confirmed immunohistochemically, and both HPLCs and cell line 1-11 expressed mRNA from the TGF-ß1, TGF-ß type I receptor, and TGF-ß type II receptor genes. Although exogenous TGF-ß1 stimulated the proliferation of HPLCs, it did not upregulate the expression of alpha-smooth muscle actin (α-SMA), type I collagen (Col I), or fibrillin-1 (FBN1) mRNA or of α-SMA protein in HPLCs, whereas expression for these genes was attenuated by an anti-TGF-ß1 neutralizing antibody. In contrast, exogenous TGF-ß1 reduced the proliferation of cell line 1-11, although it upregulated the expression of α-SMA, Col I, and FBN1 mRNA and of α-SMA protein in this cell line. In addition, interleukin-1 beta stimulation significantly reduced the expression of TGF-ß1 mRNA and protein in HPLCs. Thus, TGF-ß1 seems to play an important role in inducing fibroblastic differentiation of PDL stem/progenitor cells and in maintaining the PDL apparatus under physiological conditions.