Effects of TGF-β1 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-β1 (TGF-β1) is a multifunctional cytokine, but little is known about the effects of TGF-β1 on PDL cells. Our aim has been to demonstrate the expression of TGF-β1 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-β1 in the entire PDL tissue was confirmed immunohistochemically, and both HPLCs and cell line 1-11 expressed mRNA from the TGF-β1, TGF-β type I receptor, and TGF-β type II receptor genes. Although exogenous TGF-β1 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-β1 neutralizing antibody. In contrast, exogenous TGF-β1 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-β1 mRNA and protein in HPLCs. Thus, TGF-β1 seems to play an important role in inducing fibroblastic differentiation of PDL stem/progenitor cells and in maintaining the PDL apparatus under physiological conditions.

Transforming growth factor beta-1 expression in macrophages of human chronic periapical diseases

“…It also exerts inhibitory and stimulatory effects on bone marrow cells (Jacobsen et al, 1993) TGF-b1 has high chemotactic activities on osteoblasts and can stimulate the proliferation and differentiation of mesenchymal stem cells to promote the synthesis of osteoblasts, chondroblasts, and extracellular matrix (Kingsley, 1994;Fox and Lovibond, 2005;Hu et al, 2011). TGF-b1 appears to play an important role in inducing fibroblastic differentiation of periodontal ligament (PDL) stem/progenitor cells and in maintaining the PDL apparatus under physiological conditions (Fujii et al, 2010). It also regulates the expression of collagen type I and promotes tissue healing (Okubo et al, 2003;Fujita et al, 2004;Ono et al, 2007).…”

“…However, reports on the effect of TGF-b1 in periapical inflammation are scarce (Khalil et al, 1989). Fujii et al (2010) suggested that TGF-b1 is involved in the incidence, development, and tissue repair in rat experimental periodontal disease; however, the expression and the possible mechanism via which TGF-b1 effects MPs in human periodontal disease is unknown. In this study, double immunofluorescence (DIF) was used to determine the levels of TGF-b1 in MPs of human periodontal disease, and its role in the pathology of the disease and tissue repair was also investigated.…”

Assessment of an Efficient Xeno-Free Culture System of Human Periodontal Ligament Stem Cells

“…Furthermore, the synthesis of TGFb1 in PDL cells depended on their differentiation stage and could contribute to the differentiation of immature PDL cells into functional PDL fibroblasts. 55 However, TGFb1 also blocked osteogenesis by various mechanisms depending on its concentration, cell density, and differentiation stage of the cells; in particular, it inhibited osteoblast differentiation via suppression of IGF1 expression and subsequent downregulation of the PI3K/Akt pathway. In fact, during osteogenic commitment, it appeared to stimulate the proliferation and development of early osteoblasts, but inhibited their maturation and mineralization, and, consequently, the differentiation process was associated with a decrease of TGFb.…”

Differential effects of TGF-β1 and FGF-2 on SDF-1α expression in human periodontal ligament cells derived from deciduous teeth in vitro

“…At present, bioactive soluble factors such as cytokines and growth factors are being evaluated for clinical use in the regeneration of periodontal tissue damaged or lost due to periodontitis. Of these factors, both the basic fibroblast growth factor (FGF-2) and the transforming growth factor (TGF)-β1 are multifunctional growth factors that have various effects, including the induction of proliferation and differentiation of a wide range of mesodermal and neuroectodermal cells (10,11). However, their effects on SDF-1α expression in PDL cells are currently unknown.…”