Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures.

PTH was studied for its effects on bone formation in cultured rat calvariae. 0.01-10 nM PTH stimulated [3H]thymidine incorporation into DNA by up to 4.8-fold. Although continuous treatment with PTH for 24-72 h inhibited [3H]proline incorporation into collagen, transient (24 h) treatment enhanced [3H]proline incorporation into collagen 24-48 h after the hormone was removed. The collagen stimulated by PTH was type I and the effect was observed in the periosteum-free bone and was not blocked by hydroxyurea. Furthermore, treatment with 1-100 nM PTH for 24 h increased insulin-like growth factor (IGF) I concentrations by two to fourfold, and an IGF I antibody prevented the PTH stimulation of collagen synthesis, but not its mitogenic effect. In conclusion, continuous treatment with PTH inhibits calvarial collagen, whereas transient treatment stimulates collagen synthesis, and the stimulatory effect is mediated by local production of IGF I.

[1]  D. V. Cohn,et al.  Target cells in bone for parathormone and calcitonin are different: enrichment for each cell type by sequential digestion of mouse calvaria and selective adhesion to polymeric surfaces. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[2]  B. Peterkofsky,et al.  The effect of ascorbic acid on collagen polypeptide synthesis and proline hydroxylation during the growth of cultured fibroblasts. , 1972, Archives of biochemistry and biophysics.

[3]  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.

[4]  Birgitta,et al.  An antibody that blocks insulin-like growth factor (IGF) binding to the type II IGF receptor is neither an agonist nor an inhibitor of IGF-stimulated biologic responses in L6 myoblasts. , 1987, The Journal of biological chemistry.

[5]  J. Potts,et al.  Short-term effects of synthetic human parathyroid hormone-(1--34) administration on bone mineral metabolism in osteoporotic patients. , 1981, The Journal of clinical investigation.

[6]  J. A. Parsons CHAPTER 5 – Parathyroid Physiology and the Skeleton , 1976 .

[7]  E. Froesch,et al.  Growth hormone dependent stimulation of osteoblast-like cells in serum-free cultures via local synthesis of insulin-like growth factor I. , 1988, Biochemical and biophysical research communications.

[8]  E. Canalis,et al.  Insulin-like growth factor I has independent effects on bone matrix formation and cell replication. , 1988, Endocrinology.

[9]  R. Furlanetto,et al.  The type II insulin-like growth factor receptor does not mediate deoxyribonucleic acid synthesis in human fibroblasts. , 1987, The Journal of clinical endocrinology and metabolism.

[10]  J. Heersche,et al.  Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermittent and continuous administration. , 1982, Endocrinology.

[11]  R. Russell,et al.  Parathyroid hormone stimulates the proliferation of cells derived from human bone. , 1986, Endocrinology.

[12]  E. Canalis,et al.  Transforming growth factor beta is a bifunctional regulator of replication and collagen synthesis in osteoblast-enriched cell cultures from fetal rat bone. , 1987, The Journal of biological chemistry.

[13]  L. Raisz BONE RESORPTION IN TISSUE CULTURE. FACTORS INFLUENCING THE RESPONSE TO PARATHYROID HORMONE. , 1965, The Journal of clinical investigation.

[14]  E. Canalis,et al.  Parathyroid hormone modulates transforming growth factor beta activity and binding in osteoblast-enriched cell cultures from fetal rat parietal bone. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[15]  E. Canalis,et al.  Isolation and characterization of insulin-like growth factor I (somatomedin-C) from cultures of fetal rat calvariae. , 1988, Endocrinology.

[16]  B. Sykes,et al.  The estimation of two collagens from human dermis by interrupted gel electrophoresis. , 1976, Biochemical and biophysical research communications.

[17]  G. Howard,et al.  Parathyroid hormone stimulates bone formation and resorption in organ culture: evidence for a coupling mechanism. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[18]  E. Canalis,et al.  Effect of insulinlike growth factor I on DNA and protein synthesis in cultured rat calvaria. , 1980, The Journal of clinical investigation.

[19]  J. Hock,et al.  DNA synthesis is not necessary for osteoclastic responses to parathyroid hormone in cultured fetal rat long bones. , 1983, The Journal of clinical investigation.

[20]  J. Hock,et al.  Human parathyroid hormone-(1-34) increases bone mass in ovariectomized and orchidectomized rats. , 1988, Endocrinology.

[21]  S. Birge,et al.  Bone Cells: Biochemical and Biological Studies after Enzymatic Isolation , 1964, Science.

[22]  E. Canalis,et al.  Hormonal control of bone collagen synthesis in vitro: effects of parathyroid hormone and calcitonin. , 1976, Endocrinology.

[23]  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.

[24]  E. Canalis,et al.  Growth factors and the regulation of bone remodeling. , 1988, The Journal of clinical investigation.

[25]  E. Canalis,et al.  The hormonal and local regulation of bone formation. , 1983, Endocrine reviews.

[26]  W. Russell,et al.  Inhibition of the mitogenic effects of plasma by a monoclonal antibody to somatomedin C. , 1984, Proceedings of the National Academy of Sciences of the United States of America.