Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1989 Jan;83(1):60–65. doi: 10.1172/JCI113885

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

E Canalis 1, M Centrella 1, W Burch 1, T L McCarthy 1
PMCID: PMC303643  PMID: 2910920

Abstract

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.

Full text

PDF
61

Images in this article

63Image
on p.63

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Canalis E. Effect of insulinlike growth factor I on DNA and protein synthesis in cultured rat calvaria. J Clin Invest. 1980 Oct;66(4):709–719. doi: 10.1172/JCI109908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Canalis E., McCarthy T., Centrella M. Growth factors and the regulation of bone remodeling. J Clin Invest. 1988 Feb;81(2):277–281. doi: 10.1172/JCI113318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Canalis E., McCarthy T., Centrella M. Isolation and characterization of insulin-like growth factor I (somatomedin-C) from cultures of fetal rat calvariae. Endocrinology. 1988 Jan;122(1):22–27. doi: 10.1210/endo-122-1-22. [DOI] [PubMed] [Google Scholar]
  4. Canalis E. The hormonal and local regulation of bone formation. Endocr Rev. 1983 Winter;4(1):62–77. doi: 10.1210/edrv-4-1-62. [DOI] [PubMed] [Google Scholar]
  5. Centrella M., Canalis E. Transforming and nontransforming growth factors are present in medium conditioned by fetal rat calvariae. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7335–7339. doi: 10.1073/pnas.82.21.7335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Centrella M., McCarthy T. L., Canalis E. Parathyroid hormone modulates transforming growth factor beta activity and binding in osteoblast-enriched cell cultures from fetal rat parietal bone. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5889–5893. doi: 10.1073/pnas.85.16.5889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Centrella M., McCarthy T. L., Canalis E. Transforming growth factor beta is a bifunctional regulator of replication and collagen synthesis in osteoblast-enriched cell cultures from fetal rat bone. J Biol Chem. 1987 Feb 25;262(6):2869–2874. [PubMed] [Google Scholar]
  8. Dietrich J. W., Canalis E. M., Maina D. M., Raisz L. G. Hormonal control of bone collagen synthesis in vitro: effects of parathyroid hormone and calcitonin. Endocrinology. 1976 Apr;98(4):943–949. doi: 10.1210/endo-98-4-943. [DOI] [PubMed] [Google Scholar]
  9. Ernst M., Froesch E. R. Growth hormone dependent stimulation of osteoblast-like cells in serum-free cultures via local synthesis of insulin-like growth factor I. Biochem Biophys Res Commun. 1988 Feb 29;151(1):142–147. doi: 10.1016/0006-291x(88)90570-0. [DOI] [PubMed] [Google Scholar]
  10. Furlanetto R. W., DiCarlo J. N., Wisehart C. The type II insulin-like growth factor receptor does not mediate deoxyribonucleic acid synthesis in human fibroblasts. J Clin Endocrinol Metab. 1987 Jun;64(6):1142–1149. doi: 10.1210/jcem-64-6-1142. [DOI] [PubMed] [Google Scholar]
  11. Hock J. M., Centrella M., Canalis E. Insulin-like growth factor I has independent effects on bone matrix formation and cell replication. Endocrinology. 1988 Jan;122(1):254–260. doi: 10.1210/endo-122-1-254. [DOI] [PubMed] [Google Scholar]
  12. Hock J. M., Gera I., Fonseca J., Raisz L. G. Human parathyroid hormone-(1-34) increases bone mass in ovariectomized and orchidectomized rats. Endocrinology. 1988 Jun;122(6):2899–2904. doi: 10.1210/endo-122-6-2899. [DOI] [PubMed] [Google Scholar]
  13. Howard G. A., Bottemiller B. L., Turner R. T., Rader J. I., Baylink D. J. Parathyroid hormone stimulates bone formation and resorption in organ culture: evidence for a coupling mechanism. Proc Natl Acad Sci U S A. 1981 May;78(5):3204–3208. doi: 10.1073/pnas.78.5.3204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kiess W., Haskell J. F., Lee L., Greenstein L. A., Miller B. E., Aarons A. L., Rechler M. M., Nissley S. P. 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. J Biol Chem. 1987 Sep 15;262(26):12745–12751. [PubMed] [Google Scholar]
  15. Lorenzo J. A., Raisz L. G., Hock J. M. DNA synthesis is not necessary for osteoclastic responses to parathyroid hormone in cultured fetal rat long bones. J Clin Invest. 1983 Dec;72(6):1924–1929. doi: 10.1172/JCI111156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. MacDonald B. R., Gallagher J. A., Russell R. G. Parathyroid hormone stimulates the proliferation of cells derived from human bone. Endocrinology. 1986 Jun;118(6):2445–2449. doi: 10.1210/endo-118-6-2445. [DOI] [PubMed] [Google Scholar]
  17. PECK W. A., BIRGE S. J., Jr, FEDAK S. A. BONE CELLS: BIOCHEMICAL AND BIOLOGICAL STUDIES AFTER ENZYMATIC ISOLATION. Science. 1964 Dec 11;146(3650):1476–1477. doi: 10.1126/science.146.3650.1476. [DOI] [PubMed] [Google Scholar]
  18. Peterkofsky B., Diegelmann R. Use of a mixture of proteinase-free collagenases for the specific assay of radioactive collagen in the presence of other proteins. Biochemistry. 1971 Mar 16;10(6):988–994. doi: 10.1021/bi00782a009. [DOI] [PubMed] [Google Scholar]
  19. Peterkofsky B. The effect of ascorbic acid on collagen polypeptide synthesis and proline hydroxylation during the growth of cultured fibroblasts. Arch Biochem Biophys. 1972 Sep;152(1):318–328. doi: 10.1016/0003-9861(72)90221-4. [DOI] [PubMed] [Google Scholar]
  20. RAISZ L. G. BONE RESORPTION IN TISSUE CULTURE. FACTORS INFLUENCING THE RESPONSE TO PARATHYROID HORMONE. J Clin Invest. 1965 Jan;44:103–116. doi: 10.1172/JCI105117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Russell W. E., Van Wyk J. J., Pledger W. J. Inhibition of the mitogenic effects of plasma by a monoclonal antibody to somatomedin C. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2389–2392. doi: 10.1073/pnas.81.8.2389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Slovik D. M., Neer R. M., Potts J. T., Jr Short-term effects of synthetic human parathyroid hormone-(1--34) administration on bone mineral metabolism in osteoporotic patients. J Clin Invest. 1981 Nov;68(5):1261–1271. doi: 10.1172/JCI110372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Slovik D. M., Rosenthal D. I., Doppelt S. H., Potts J. T., Jr, Daly M. A., Campbell J. A., Neer R. M. Restoration of spinal bone in osteoporotic men by treatment with human parathyroid hormone (1-34) and 1,25-dihydroxyvitamin D. J Bone Miner Res. 1986 Aug;1(4):377–381. doi: 10.1002/jbmr.5650010411. [DOI] [PubMed] [Google Scholar]
  24. Sykes B., Puddle B., Francis M., Smith R. The estimation of two collagens from human dermis by interrupted gel electrophoresis. Biochem Biophys Res Commun. 1976 Oct 18;72(4):1472–1480. doi: 10.1016/s0006-291x(76)80180-5. [DOI] [PubMed] [Google Scholar]
  25. Tam C. S., Heersche J. N., Murray T. M., Parsons J. A. Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermittent and continuous administration. Endocrinology. 1982 Feb;110(2):506–512. doi: 10.1210/endo-110-2-506. [DOI] [PubMed] [Google Scholar]
  26. Wong G. L., Cohn D. V. 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. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3167–3171. doi: 10.1073/pnas.72.8.3167. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES