Prednisolone induces osteoporosis-like phenotype in regenerating zebrafish scales
Tóm tắt
We demonstrate that glucocorticoids induce an osteoporotic phenotype in regenerating scales of zebrafish. Exposure to prednisolone results in altered mineral content, enhanced matrix breakdown, and an osteoporotic gene-expression profile in osteoblasts and osteoclasts. This highlights that the zebrafish scale provides a powerful tool for preclinical osteoporosis research. This study aims to evaluate whether glucocorticoid (prednisolone) treatment of zebrafish induces an osteoporotic phenotype in regenerating scales. Scales, a readily accessible dermal bone tissue, may provide a tool to study direct osteogenesis and its disturbance by glucocorticoids. In adult zebrafish, treated with 25 μM prednisolone phosphate via the water, scales were removed and allowed to regenerate. During regeneration scale morphology and the molar calcium/phosphorus ratio in scales were assessed and osteoblast and osteoclast activities were monitored by time profiling of cell-specific genes; mineralization was visualized by Von Kossa staining, osteoclast activity by tartrate-resistant acid phosphatase histochemistry. Prednisolone (compared to controls) enhances osteoclast activity and matrix resorption and slows down the build up of the calcium/phosphorus molar ratio indicative of altered crystal maturation. Prednisolone treatment further impedes regeneration through a shift in the time profiles of osteoblast and osteoclast genes that commensurates with an osteoporosis-like imbalance in bone formation. A glucocorticoid-induced osteoporosis phenotype as seen in mammals was induced in regenerating scalar bone of zebrafish treated with prednisolone. An unsurpassed convenience and low cost then make the zebrafish scale a superior model for preclinical studies in osteoporosis research.
Tài liệu tham khảo
Mugiya Y, Watabe N (1977) Studies on fish scale formation and resorption. II. Effect of estradiol on calcium homeostasis and skeletal tissue resorption in the goldfish, Carassius auratus, and the killifish, Fundulus heteroclitus. Comp Biochem Phys A 57:197–202
Flik G, Fenwick JC, Kolar Z, Mayer-Gostan N, Wendelaar Bonga SE (1986) Effects of low ambient calcium levels on wholebody Ca2+ flux rates and internal calcium pools in the freshwater cichlid teleost, Oreochromis mossambicus. J Exp Biol 120:249–264
de Vrieze E, Sharif F, Metz JR, Flik G, Richardson MK (2011) Matrix metalloproteinases in osteoclasts of ontogenetic and regenerating zebrafish scales. Bone 48:704–712
Sire J-Y (1989) The same cell lineage is involved in scale formation and regeneration in the teleost fish Hemichromis bimaculatus. Tissue and Cell 21:447–462
Metz JR, de Vrieze E, Lock EJ, Schulten IE, Flik G (2012) Elasmoid scales of fishes as model in biomedical bone research. J App Ichthyol 28:382–387
Bereiter-Hahn J, Zylberberg L (1993) Regeneration of teleost fish scale. Comp Biochem Phys A 105:625–641
Ohira Y, Shimizu M, Ura K, Takagi Y (2007) Scale regeneration and calcification in goldfish Carassius auratus: quantitative and morphological processes. Fisheries Sci 73:46–54
de Vrieze E, Heijnen L, Metz JR, Flik G (2012) Evidence for a hydroxyapatite precursor in regenerating cyprinid scales. J Appl Ichthyol 28:388–392
Fonseca VG, Laizé V, Valente MS, Cancela ML (2007) Identification of an osteopontin-like protein in fish associated with mineral formation. FEBS J 274:4428–4439
Nishimoto SK, Waite JH, Nishimoto M, Kriwacki RW (2003) Structure, activity, and distribution of fish osteocalcin. J Biol Chem 278:11843–11848
Zylberberg L, Bereiter-Hahn J, Sire J-Y (1988) Cytoskeletal organization and collagen orientation in the fish scales. Cell Tissue Res 253:597–607
Kimura S, Miyauchi Y, Uchida N (1991) Scale and bone type I collagens of carp (Cyprinus carpio). Comp Biochem Phys B 99:473–476
de Vrieze E, Metz JR, Von den Hoff JW, Flik G (2010) ALP, TRAcP and cathepsin K in elasmoid scales: a role in mineral metabolism? J Appl Ichthyol 26:210–213
Rissanen JP, Halleen JM (2010) Models and screening assays for drug discovery in osteoporosis. Expert Opin Drug Dis 5:1163–1174
Gomes PS, Fernandes MH (2011) Rodent models in bone-related research: the relevance of calvarial defects in the assessment of bone regeneration strategies. Lab Anim 45:14–24
Suzuki N, Hattori A (2003) Bisphenol A suppresses osteoclastic and osteoblastic activities in the cultured scales of goldfish. Life Sci 73:2237–2247
Brittijn S, Duivesteijn S, Belmamoune M, Bertens L, Bitter W, de Bruijn J, Champagne D, Cuppen E, Flik G, Vandenbroucke-Grauls C, Janssen R, de Jong I, de Kloet E, Kros A, Meijer A, Metz J, van der Sar A, Schaaf M, Schulte-Merker S, Spaink H, Tak P, Verbeek F, Vervoordeldonk M, Vonk F, Witte F, Yuan H, Richardson M (2009) Zebrafish development and regeneration: new tools for biomedical research. Int J Dev Biol 53:835–850
Suzuki N, Danks JA, Maruyama Y, Ikegame M, Sasayama Y, Hattori A, Nakamura M, Tabata MJ, Yamamoto T, Furuya R, Saijoh K, Mishima H, Srivastav AK, Furusawa Y, Kondo T, Tabuchi Y, Takasaki I, Chowdhury VS, Hayakawa K, Martin TJ (2011) Parathyroid hormone 1 (1–34) acts on the scales and involves calcium metabolism in goldfish. Bone 48:1186–1193
Pasqualetti S, Banfi G, Mariotti M (2012) Osteoblast and osteoclast behavior in zebrafish cultured scales. Cell and Tissue Research 350:69–75
McMahon M, Gerich J, Rizza R (1988) Effects of glucocorticoids on carbohydrate metabolism. Diabetes Metab Rev 4:17–30
Moutsatsou P, Kassi E, Papavassiliou AG (2012) Glucocorticoid receptor signaling in bone cells. Trends Mol Med 18:348–359
Weinstein RS (2011) Clinical practice. Glucocorticoid-induced bone disease. New Engl J Med 365:62–70
Barrett R, Chappell C, Quick M, Fleming A (2006) A rapid, high content, in vivo model of glucocorticoid-induced osteoporosis. Biotechnol J 1:651–655
Witten PE, Hansen A, Hall BK (2001) Features of mono- and multinucleated bone resorbing cells of the zebrafish (Danio rerio) and their contribution to skeletal development, remodeling, and growth. J Morphol 250:197–207
Alsop D, Vijayan MM (2008) Development of the corticosteroid stress axis and receptor expression in zebrafish. Am J Physiol Reg I 294:R711–719
Seferos N, Kotsiou A, Petsaros S, Rallis G, Tesseromatis C (2010) Mandibular bone density and calcium content affected by different kind of stress in mice. J Musculoskelet Neuronal Interact 10:231–236
Canalis E, Mazziotti G, Giustina A, Bilezikian JP (2007) Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporosis Int 18:1319–1328
Yoshikubo H, Suzuki N, Takemura K, Hoso M, Yashima S, Iwamuro S, Takagi Y, Tabata MJ, Hattori A (2005) Osteoblastic activity and estrogenic response in the regenerating scale of goldfish, a good model of osteogenesis. Life Sci 76:2699–2709
Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3:research0034.0031–research0034.0011
Schaaf MJM, Chatzopoulou A, Spaink HP (2009) The zebrafish as a model system for glucocorticoid receptor research. Comp Biochem Phys A 153:75–82
Huitema LF, Apschner A, Logister I, Spoorendonk KM, Bussmann J, Hammond CL, Schulte-Merker S (2012) Entpd5 is essential for skeletal mineralization and regulates phosphate homeostasis in zebrafish. P Natl Acad Sci USA 109:21372–21377
Hofbauer LC, Kuhne CA, Viereck V (2004) The OPG/RANKL/RANK system in metabolic bone diseases. J Musculoskelet Neuronal Interact 4:268–275
Persson P, Sundell K, Björnsson BT (1994) Estradiol-17β-induced calcium uptake and resorption in juvenile rainbow trout, Oncorhynchus mykiss. Fish Physiol Biochem 5:379–386
Armour KJ, Lehane DB, Pakdel F, Valotaire Y, Graham R, Russell G, Henderson IW (1997) Estrogen receptor mRNA in mineralized tissues of rainbow trout: calcium mobilization by estrogen. FEBS Lett 411:145–148
Hofbauer LC, Zeitz U, Schoppet M, Skalicky M, Schuler C, Stolina M, Kostenuik PJ, Erben RG (2009) Prevention of glucocorticoid-induced bone loss in mice by inhibition of RANKL. Arthritis Rheum 60:1427–1437
Sire J-Y, Huysseune A, Meunier FJ (1990) Osteoclasts in teleost fish: light- and electron-microscopical observations. Cell Tissue Res 260:85–94
Witten PE, Huysseune A (2009) A comparative view on mechanisms and functions of skeletal remodelling in teleost fish, with special emphasis on osteoclasts and their function. Biol Rev 315–346
Yao W, Cheng Z, Busse C, Pham A, Nakamura MC, Lane NE (2008) Glucocorticoid excess in mice results in early activation of osteoclastogenesis and adipogenesis and prolonged suppression of osteogenesis: a longitudinal study of gene expression in bone tissue from glucocorticoid-treated mice. Arthritis Rheum 58:1674–1686
Schönbörner AA, Boivin G, Baud CA (1979) The mineralization processes in teleost fish scales. Cell Tissue Res 202:203–212
Dorozhkin SV (2007) Calcium orthophosphates. J Mater Sci 42:1061–1095
Mahamid J, Sharir A, Addadi L, Weiner S (2008) Amorphous calcium phosphate is a major component of the forming fin bones of zebrafish: indications for an amorphous precursor phase. P NatlAcad Sci USA 105:12748–12753
Migliaccio S, Brama M, Malavolta N (2009) Management of glucocorticoids-induced osteoporosis: role of teriparatide. Ther Clin Risk Manag 5(2):305–310
Brabnikova Maresova K, Pavelka K, Stepan JJ (2013) Acute effects of glucocorticoids on serum markers of osteoclasts, osteoblasts, and osteocytes. Calcif Tissue Int 92:354–361
Knopf F, Hammond C, Chekuru A, Kurth T, Hans S, Weber CW, Mahatma G, Fisher S, Brand M, Schulte-Merker S, Weidinger G (2011) Bone regenerates via dedifferentiation of osteoblasts in the zebrafish fin. Dev Cell 20:713–724
Aubin JE, Liu F, Malaval L, Gupta AK (1995) Osteoblast and chondroblast differentiation. Bone 17:77S–83S
Bjarnason NH, Hassager C, Christiansen C (1998) Postmenopausal bone remodelling and hormone replacement. Climacteric 1:72–79
Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102:274–282
Hofbauer LC, Gori F, Riggs BL, Lacey DL, Dunstan CR, Spelsberg TC, Khosla S (1999) Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology 140:4382–4389
Humphrey EL, Williams JH, Davie MW, Marshall MJ (2006) Effects of dissociated glucocorticoids on OPG and RANKL in osteoblastic cells. Bone 38:652–661
Cortet B (2011) Bone repair in osteoporotic bone: postmenopausal and cortisone-induced osteoporosis. Osteoporosis Int 22:2007–2010