Abstract
Clinical observations suggest that the onset and severity of glucocorticoid (GC) induced osteoporosis is dependent on the duration of the GC treatment and the applied GC compound. To test whether these in vivo observations are reflected by different in vitro effects of various synthetic GCs on human bone cell metabolism we isolated human osteoblast-like cells (HOC) from bone biopsies of healthy (no clinical symptoms of arthritis or arthrosis) adults who underwent selective orthopedic surgery. HOC were identified as bone cells by 1,25-vitamin D3-stimulated increase of specific alkaline phosphatase (ALP) activity, secretion of osteocalcin and type-I procollagen peptide, and the ability to form mineral in vitro. We investigated the effects of dexamethasone (dexa), methylprednisolone (mpred), prednisolone (pred), and deflazacort (defla) on DNA-synthesis, ALP, and osteocalcin (OC)- and type-I procollagen peptide secretion of HOC in vitro. In summary, (1) GC exposure stimulates DNA synthesis after 6–12-hour treatment periods; (2) dex and mpred strongly inhibit DNA (48-hour treatment) and collagen synthesis but stimulate ALP, whereas pred and defla exhibit smaller effects on DNA synthesis, ALP, and collagen production; and (3) all tested glucocorticoids inhibit OC secretion by HOC in vitro. Thus, the effect of GC on DNA synthesis of HOC varies with the duration of GC exposure, and dex and mpred more potently affect HOC metabolism in vitro than pred and defla.
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References
Baylink DJ (1983) Glucocorticoid-induced osteoporosis. N Engl J Med 309:306–308
Reid IR, Evans MC, Stapleton J (1992) Lateral spine densitometry is a more sensitive indicator of glucocorticoid-induced bone loss. J Bone Miner Res 7:1221–1225
Dempster DW (1989) Bone histomorphometry in glucocorticoid-induced osteoporosis. J Bone Miner Res 4:137–141
Ortoft G, Oxlund H (1988) Reduced strength of rat cortical bone after glucocorticoid treatment. Calcif Tissue Int 43:376–382
Caniggia A, Lore F, Nuti R, Vattimo A (1984) Glucocorticoids and intestinal absorption of calcium and phosphate. Adv Exp Biol Med 171:91–100
Ritz E, Kreusser W, Rambausek M (1984) Effects of glucocorticoids on calcium and phosphate excretion. Adv Exp Biol Med 171:381–397
Teitelbaum S, Bar Z, Fallon MD, Imbimbo C, Malone JD, Kahn AJ (1984) Glucocorticoids and bone resorption. Adv Exp Biol Med 171:121–129
Lukert BP, Raisz LG (1990) Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Int Med 112:352–364
Hahn TJ, Halstead LR, Strates B, Imbimbo B, Baran DT (1980) Comparison of subacute effects of oxazacort and prednisone on mineral metabolism in man. Calcif Tissue Int 31:109–115
Olgaard K, Storm T, Wowern N, Daugaard H, Egfjord M, Lewin E, Brandi L (1992) Glucocorticoid-induced osteoporosis in the lumbar spine, forearm, and mandible of nephrotic patients: a double-blind study on the high-dose, long-term effects of prednisone versus deflazacort. Calcif Tissue Int 50:490–497
Messina OD, Barrauja JC, Zanchetta JR, Maldonado JA, Bogado CE, Sebastian ON, Flores D, Riopedre AM, Redondo G, Lazaro A (1992) Effect of low doses of deflazacort vs prednisone on bone mineral content in premenopausal rheumatoid arthritis. J Rheumatol 19:1520–1526
Loftus J, Allen R, Hesp R, Reid DM, Wright DJ, Green JR, Reeve J, Ansell BM, Woo PM (1991) Randomized, double-blind trial of deflazacort versus prednisone in juvenile chronic arthritis: a relatively bone-sparing effect of deflazacort. Pediatrics 88:428–436
Gray R, Harrington C, Coulton L, Calloway J, Broe M, Kanis J (1990) Long-term treatment of chronic inflammatory disorders with deflazacort. J Orthop Rheumatol 3:15–27
Gennari C, Imbimbo C (1985) Effects of prednisone and deflazacort on vertebral bone mass. Calcif Tissue Int 37:592–593
Farley JR, Chesnut CH, Baylink DJ (1981) Clin Chem 27:2002–2007
Wergedal JE, Matsuyama T, Strong DD (1992) Differentiation or normal human bone cells by transforming growth factor beta and 1,25(OH)2vitamin D3. Metabolism 41:42–48
Johansen JS, Williamson MK, Rice JS, Price PA (1992) Identification of proteins secreted by human osteoblastic cells in culture. J Bone Miner Res 7:501–512
Dietrich W, Canalis EM, Maina DM, Raisz LG (1979) Effects of glucocorticoids on fetal rat bone collagen synthesis in vitro. Endocrinology 104:715–721
Canalis E (1983) Effect of glucocorticoids on type I collagen synthesis, alkaline phosphatase activity, and deoxyribonucleic acid content in cultured rat calvariae. Endocrinology 112:931–939
Wong GL (1979) Basal activities and hormone responsiveness of osteoclast-like and osteoblast-like bone cells are regulated by glucocorticoids. J Biol Chem 254:6337
Nielsen HK, Brixen K, Kassem M, Mosekilde L (1991) Acute effect of 1,25-dihydroxyvitamin D3, prednisone, and 1,25-dihydroxyvitamin D3 plus prednisone on serum osteocalcin in normal individuals. J Bone Miner Res 6:435–441
Guenther HL, Felix R, Fleisch H (1984) Comparative study of deflazacort, a new synthetic corticosteroid, and dexamethasone on the synthesis of collagen in different rat bone cell populations and rabbit articular chondrocytes. Calcif Tissue Int 36:145–152
Lund B, Pedersen JG, Egsmose (1984) In vitro evidence of the calcium-sparing effect of deflazacort. Adv Exp Biol Med 171: 149–154
Canalis E, Avioli L (1992) Effects of deflazacort on aspects of bone formation in cultures of intact calvariae and osteoblast-enriched cells. J Bone Miner Res 7:1085–1092
Chyun YS, Kream BE, Raisz LG (1984) Cortisol decreases bone formation by inhibiting periosteal cell proliferation. Endocrinology 114:1–4
Hahn TJ, Westbrook SL, Halstead LR (1984) Cortisol modulation of osteoblast metabolic activity in cultured neonatal rat bone. Endocrinology 114:1864–1870
Rath NC, Reddi AW (1979) Influence of adrenalectomy and dexamethasone on matrix-induced endochondral bone differentiation. Endocrinology 104:1698
Canalis E (1984) Effect of cortisol on periosteal and nonperiosteal collagen and DNA synthesis in cultured rat calvariae. Calcif Tissue Int 36:158–166
Gallagher JA, Beresford JN, McGuire MKB, Ebsworth NM, Meats JE, Gowen M, Elford P, Wright D, Poser J, Coulton LA, Sharrard M, Imbimbo B, Kanis JA, Russell RGG (1984) Effects of glucocorticoids and anabolic steroids on cells derived from human skeletal and articular tissues in vitro. Adv Exp Biol Med 171:279–291
Chen TL, Cone CM, Feldman D (1983) Glucocorticoid modulation of cell proliferation in cultured osteoblast-like bone cells: differences between rat and mouse. Endocrinology 112:1739–1745
Wong M, Rao LG, Ly H, Hamilton L, Tong J, Sturtridge W, McBroom R, Aubin JE, Murray TM (1990) Long-term effects of physiologic concentrations of dexamethasone on human bone-derived cells. J Bone Miner Res 5:803–813
Webb DK, Moulton BC, Khan SA (1993) Estrogen induces expression of c-jun and jun-B protooncogenes in specific rat uterine cells. Endocrinology 133:20–28
Okazaki R, Ikeda K, Sakamoto A, Nakano T, Morimoto K, Kikuchi T, Urakawa K, Ogata E, Matsumoto T (1992) Transcriptional activation of c-fos and c-jun protooncogenes by serum growth factors in osteoblast-like MC3T3-E1 cells. J Bone Miner Res 7:1149–1155
Schüle R, Rangarajan P, Kliewer S, Ransone LJ, Bolado J, Yang N, Verma IM, Evans RM (1990) Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell 62:1217–1226
Yang-Yen H, Chambard J, Sun Y, Smeal T, Schmidt TJ, Drouin J, Karin M (1990) Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein intercation. Cell 62:1205–1215
Jonat C, Rahmsdorf HJ, Park K, Cato A, Gabel S, Ponta H, Herrlich P (1990) Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell 62:1189–1204
McCarthy TL, Centrella M, Canalis E (1990) Cortisol inhibits the synthesis of insulin-like growth factor I in skeletal cells. Endocrinology 126:1569–1575
Firek AF, Strong DD, Linkhart TA, Jennings JC (1992) Dexamethasone reduces basal and transforming growth factor beta 1 autoinduced TGFβ1 release by normal human osteoblast-like cells. Endocrine Society, 74th Annual Meeting (abstract) p 155
Price WA, Stiles AD, Moats-Staats BM, D'Ercole AJ (1992) Gene expression of insulin-like growth factors, the type I IGF receptor, and IGF-binding proteins in dexamethasone-induced fetal growth retardation. Endocrinology 130:1424–1432
Unterman TG, Phillips LS (1985) Glucocorticoid effects on somatomedins and somatomedin inhibitors. J Clin Endocrinol Metab 61:618–626
Canalis E (1983) Effect of glucocorticoids on type I collagen synthesis, alkaline phosphatase activity, and deoxyribonucleic acid content in cultured rat calvariae. Endocrinology 112:931–939
Peck WA (1984) The effects of glucocorticoids on bone cell metabolism and function. Adv Exp Biol Med 171:111–119
Sambrook P, Birmingham J, Kempler S, Kelly P, Eberl S, Pocock N, Yeates M, Eisman J (1990) Corticosteroid effects on proximal femur bone loss. J Bone Miner Res 5:1211–1216
Srivastava D, Thompson EB (1990) Two glucocorticoid binding sites on the human glucocorticoid receptor. Endocrinology 127: 1770–1778
Nielsen KH, Charles P, Mosekilde L (1988) The effect of single oral dose of prednisolone on the circadian rhythm of serum osteocalcin in normal subjects. J Clin Endocrinol Metab 67: 1025–1030
Quarles LD (1992) Prednisone-induced osteopenia in beagles: variable effects mediated by differential suppression of bone formation. Am J Physiol 263:136–141
Puolijoki H, Liippo K, Herrala J, Salmi J, Tala E (1992) Inhaled beclomethasone decreases serum osteocalcin in postmenopausal asthmatic women. Bone 13:285–288
Morrison N, Eisman J (1993) Role of the negative glucocorticoid regulatory element in glucocorticoid repression of the human osteocalcin promoter. J Bone Miner Res 8:969–975
Li Y, Stashenko P (1993) Characterization of a tumor necrosis factor-responsive element which down-regulates the human osteocalcin gene. Mol Cell Biol 13:3714–3721
Subramaniam M, Colvard D, Keeting PE, Rasmussen K, Riggs BL (1992) Glucocorticoid regulation of alkaline phosphatase, osteocalcin, and proto-oncogenes in normal human osteoblast-like cells. J Cell Biochem 50:411–424
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Kasperk, C., Schneider, U., Sommer, U. et al. Differential effects of glucocorticoids on human osteoblastic cell metabolism in vitro . Calcif Tissue Int 57, 120–126 (1995). https://doi.org/10.1007/BF00298432
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DOI: https://doi.org/10.1007/BF00298432