Summary
The effects of cortisol on bone formation are complex and may be modulated by the presence of periosteal cells or by factors released by the periosteal tissue. To test these possibilities, cortisol was examined for its effects on the incorporation of3H-proline into collagenase-digestible protein (CDP) and noncollagen protein (NCP), on DNA synthesis and on alkaline phosphatase activity in intact and in the periosteum and nonperiosteal bone of dissected calvariae from 21-day-old fetal rats. After 24 h of treatment, cortisol increased the incorporation of3H-proline into CDP in intact bones and in the nonperiosteal bone of calvariae dissected after the culture. Cortisol inhibited the incorporation of3H-thymidine into calvarial DNA but it caused a small increase in nonperiosteal DNA content. Cortisol did not affect the incorporation of3H-proline into CDP in calvariae dissected prior to the culture if the periosteum and nonperiosteal central bone were incubated separately; the stimulatory effect was observed only if the two tissues were cultured in the same vial and were in contact. In contrast, cortisol stimulated alkaline phosphatase activity in the central nonperiosteal bone of calvariae dissected before or after the culture. After 72–96 h of treatment, cortisol inhibited the labeling of CDP, NCP, and DNA and the DNA content in intact bones and in both periosteal and nonperiosteal central bone of calvariae dissected after the culture. In contrast, when the periosteum was removed before the incubation, these inhibitory effects were observed in the periosteum and not in the nonperiosteal bone. Cortisol inhibited alkaline phosphatase activity in intact bones treated for 96 h, but removal of the periosteum resulted in a stimulatory effect in the nonperiosteal central bone. These studies indicate that 24 h treatment with cortisol stimulates collagen synthesis in nonperiosteal bone, an effect that requires the presence of periosteal tissue. Exposure to cortisol for 72–96 h inhibits collagen, noncollagen protein, and DNA synthesis, an effect that is secondary to an inhibition of periosteal cell replication. Cortisol does not cause a direct inhibition of osteoblastic function.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Peck WA, Brandt J, Miller I (1967) Hydrocortisone-induced inhibition of protein synthesis and uridine incorporation in isolated bone cellsin vitro. Proc Natl Acad Sci USA 57:1599–1606
Peck WA, Messinger K, Brandt J, Carpenter J (1969) Impaired accumulation of ribonucleic acid precursors and depletion of ribonucleic acid in glucocorticoid-treated bone cells. J Biol Chem 244:4174–4184
Chen TL, Aronow L, Feldman D (1977) Glucocorticoid receptors and inhibition of bone cell growth in primary culture. Endocrinology 100:619–628
Chen TL, Feldman D (1979) Glucocorticoid receptors and actions in subpopulations of cultured rat bone cells. Mechanism of dexamethasone potentiation of parathyroid hormone-stimulated cyclic AMP production. J Clin Invest 63:750–758
Dietrich JW, Canalis EM, Maina DM, Raisz LG (1979) Effects of glucocorticoids on fetal rat bone collagen synthesisin vitro. Endocrinology 104:715–721
Canalis E (1983) Effect of glucocorticoids on type I collagen synthesis, alkaline phosphatase activity and DNA content in cultured rat calvariae. Endocrinology 112:931–939
Peck WA, Burks JK, Wilkins J, Rodan SV, Rodan GA (1977) Evidence of preferential effects of parathyroid hormone, calcitonin and adenosine on bone and periosteum. Endocrinology 100:1357–1364
Peck WA, Birge SJ, Fedak SA (1964) Bone cells: biochemical and biological studies after enzymatic isolation. Science 146:1476–1477
Wong GL, Cohn DV (1975) 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 USA 72:3167–3171
Atkinson PR, Weidman ER, Bhaumick B, Bala RM (1981) Release of somatomedin-like activity by cultured W1-38 human fibroblasts. Endocrinology 106:2006–2012
Clemmons DR, Underwood LE, Van Wyk JJ (1980) Hormonal control of immunoreactive somatomedin production by cultured human fibroblasts. J Clin Invest 67:10–19
Canalis EM, Peck WA, Raisz LG (1980) Stimulation of DNA and collagen synthesis by autologous growth factor in cultured fetal rat calvaria. Science 210:1021–1023
Drivdahl RH, Howard GA, Baylink DJ (1982) Extracts of bone contain a potent regulator of bone formation. Biochim Biophys Acta 714:26–33
Drivdahl RH, Puzas JE, Howard GA, Baylink DJ (1981) Regulation of DNA synthesis in chick calvariae cells by factors from organ culture. Proc Soc Exp Biol Med 168:143–150
Dietrich JW, Canalis EM, Maina DM, Raisz LG (1976) Hormonal control of bone collagen synthesisin vitro. Effects of parathyroid hormone and calcitonin. Endocrinology 98:943–949
Bingham PJ, Raisz LG (1974) Bone growth in organ culture. Effects of phosphate and other nutrients on bone and cartilage. Calcif Tissue Res 14:31–48
Peterkofsky B, Diegelmann R (1971) Use of a mixture of proteinase-free collagenase for the specific assay of radioactive collagen in the presence of other proteins. Biochemistry 10:988–994
Peterkofsky B (1972) The effect of ascorbic acid on collagen polypeptide synthesis and proline hydroxylation during the growth of cultured fibroblasts. Arch Biochem Biophys 152:318–328
Kissane JM, Robbins E (1958) The fluorometric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system. J Biol Chem 233:184–188
Lowry OH (1957) Micromethods for the assay of enzymes. Methods in Enzymol 4:366–381
Canalis E (1981) Effect of hormones and growth factors on bone formationin vitro. Calcif Tissue Int 33:291
Majeska RJ, Rodan GA (1981) Hormonal regulation of alkaline phosphatase in an osteoblastic osteosarcoma cell line. Calcif Tissue Int 33:297
Wong GL (1979) Basal activities and hormone responsiveness of osteoblast-like and osteoclast-like bone cells are regulated by glucocorticoids. J Biol Chem 254:6337–6340.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Canalis, E. Effect of cortisol on periosteal and nonperiosteal collagen and DNA synthesis in cultured rat calvariae. Calcif Tissue Int 36, 158–166 (1984). https://doi.org/10.1007/BF02405312
Issue Date:
DOI: https://doi.org/10.1007/BF02405312