Effects of Transforming Growth Factor-β on Osteoblastic Osteosarcoma Cells*

Abstract

Transforming growth factor-beta (TGF beta), a polypeptide that controls growth and differentiation in many cell types and has recently been found in abundant amounts in bone, was examined for its effects on cells with the osteoblast phenotype using the clonal osteoblastic osteosarcoma cell line ROS 17/2.8. TGF beta increased alkaline phosphatase (AP) activity and the rate of collagen synthesis per cell. Cell proliferation was inhibited, and the morphological appearance of the cells was markedly changed. All effects were observed at concentrations as low as 0.1 ng/ml TGF beta. Increases in AP activity were detectable after 24 h and increased progressively with time. TGF beta increased AP activity under serum-free conditions and during thymidine-induced inhibition of DNA synthesis. The increase in AP activity mediated by TGF beta could be completely inhibited with actinomycin D and cycloheximide. 1,25-Dihydroxyvitamin D3 at 10(-7) M slightly increased AP activity in ROS 17/2.8 cells, but strongly inhibited AP activity when the cells were pretreated with TGF beta. The data suggest that TGF beta stimulates expression of the osteoblastic phenotype in ROS 17/2.8 cells and that TGF beta may be an important regulator of local bone remodeling.

Overexpression of Smad7 Blocks Primary Tumor Growth and Lung Metastasis Development in Osteosarcoma

“…Because TGFb is a cytokine widely implicated in the control of cell proliferation (17), the effect of TGFb and overexpression of Smad7 was studied on osteosarcoma cell proliferation in vitro. In contrast to previous observations that demonstrated an effect of TGFb on cell proliferation (35,36), no effect of TGFb and/or Smad7 overexpression was observed on the in vitro proliferation rate of osteosarcoma cells under our experimental conditions, suggesting that Smad7 does not directly affect the proliferation of osteosarcoma cells but rather affects the tumor microenvironment indirectly involved in the control of tumor cell proliferation.…”

Growth Factors Regulate Expression of Mineral Associated Genes in Cementoblasts

“…42,43 These differences have been attributed to several factors including concentration, 44-46 culture conditions, 47,48 maturity of cells, 49 differences in anatomic origin of cells, and animal species. 47,48,50 While promotion of cell proliferation is important for bone wound healing, several additional events must occur for periodontal repair to proceed. These include cell differentiation and biomineralization of appropriate tissues.…”

Identification of macrophage migration inhibitory factor in murine neonatal calvariae and osteoblasts

“…That is, MIF may have a function to stimulate cell proliferation and proliferation required for bone remodelling. The major growth factors synthesized by the osteoblasts include insulin-like growth factor, TGF-b, and PDGF, [30][31][32] which induce the subsequent stage of the remodelling cycle. 33 Since we found that MIF mRNA was upregulated by PDGF (unpublished observation), it is very likely that MIF may stimulate cellular proliferation in concert with growth factors.…”