Effects of Transforming Growth Factor-/? on Osteoblastic Osteosarcoma Cells*

Transforming growth factor-/? (TGF0), a poly- peptide 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 pheno- type using the clonal osteoblastic osteosarcoma cell line ROS 17/2.8. TGF/5 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/3. Increases in AP activity were detect- able after 24 h and increased progressively with time. TGF/3 increased AP activity under serum-free conditions and during thymidine-induced inhibition of DNA synthesis. The increase in AP activity mediated by TGF/3 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/3. The data suggest that TGF/3 stimulates expression of the osteoblastic phenotype in ROS 17/2.8 cells and that TGF/3 may be an important regulator of local bone remodeling. {En- docrinology 121: 212-218,1987)

[1]  D. Rowe,et al.  Hormonal regulation of collagen synthesis in a clonal rat osteosarcoma cell line. , 1986, Endocrinology.

[2]  J. McPherson,et al.  Cartilage-inducing factor-A. Apparent identity to transforming growth factor-beta. , 1986, The Journal of biological chemistry.

[3]  S. Manolagas,et al.  Phenotype-associated changes in the effects of 1,25-dihydroxyvitamin D3 on alkaline phosphatase and bone GLA-protein of rat osteoblastic cells. , 1986, Endocrinology.

[4]  M. Sporn,et al.  Type beta transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Massagué,et al.  Type beta transforming growth factor controls the adipogenic differentiation of 3T3 fibroblasts. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[6]  E. Canalis,et al.  Transforming and nontransforming growth factors are present in medium conditioned by fetal rat calvariae. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Anita B. Roberts,et al.  Human transforming growth factor-β complementary DNA sequence and expression in normal and transformed cells , 1985, Nature.

[8]  B. Kelly,et al.  Stimulation by insulin-like growth factors is required for cellular transformation by type beta transforming growth factor. , 1985, The Journal of biological chemistry.

[9]  H. Moses,et al.  Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor. , 1984, Science.

[10]  H. Moses,et al.  Specific binding to cultured cells of 125I-labeled type beta transforming growth factor from human platelets. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[11]  M. Sporn,et al.  Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney fibroblasts. , 1984, The Journal of biological chemistry.

[12]  J. Massagué.  Type beta transforming growth factor from feline sarcoma virus-transformed rat cells. Isolation and biological properties. , 1984, The Journal of biological chemistry.

[13]  Gary R. Grotendorst,et al.  Cellular transformation by coordinated action of three peptide growth factors from human platelets , 1984, Nature.

[14]  A. Roberts,et al.  Purification and properties of a type beta transforming growth factor from bovine kidney. , 1983, Biochemistry.

[15]  M. Sporn,et al.  Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. , 1983, The Journal of biological chemistry.

[16]  M. Sporn,et al.  Purification and initial characterization of a type beta transforming growth factor from human placenta. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Sporn,et al.  Polypeptide transforming growth factors isolated from bovine sources and used for wound healing in vivo. , 1983, Science.

[18]  C. B. Childs,et al.  Serum contains a platelet-derived transforming growth factor. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[19]  G. Rodan,et al.  The effect of 1,25(OH)2D3 on alkaline phosphatase in osteoblastic osteosarcoma cells. , 1982, The Journal of biological chemistry.

[20]  M. Sporn,et al.  Isolation from murine sarcoma cells of novel transforming growth factors potentiated by EGF , 1982, Nature.

[21]  J. Aubin,et al.  Isolation of bone cell clones with differences in growth, hormone responses, and extracellular matrix production , 1982, The Journal of cell biology.

[22]  M. Sporn,et al.  New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[23]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[24]  R. Diegelmann,et al.  Use of a mixture of proteinase-free collagenases for the specific assay of radioactive collagen in the presence of other proteins. , 1971, Biochemistry.

[25]  M. Sporn,et al.  Type beta transforming growth factor: a bifunctional regulator of cellular growth. , 1985, Proceedings of the National Academy of Sciences of the United States of America.