nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical Universitynefr-55Research ArticleСтатьиСТРОЕНИЕ И ФУНКЦИИ КОСТНОЙ ТКАНИ В НОРМЕ И ПРИ ПАТОЛОГИИ. СООБЩЕНИЕ IBONE TISSUE FUNCTION AND STRUCTURE UNDER NORMAL AND PATHOLOGICAL CONDITIONS. MESSAGE IСмирновА. В.SmirnovA. V.noemail@neicon.ruРумянцевА. Ш.RumyantsevA. Sh.rash.56@mail.ruПервый Санкт-Петербургский государственный медицинский университетРоссияPavlov First Saint Petersburg State Medical UniversityRussian Federation201401112014186925Copyright © Смирнов А.В., Румянцев А.Ш., 20142014Смирнов А.В., Румянцев А.Ш.Smirnov A.V., Rumyantsev A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/55

В первой части обзора рассмотрены вопросы структурной организация костной ткани, функции Wnt-протеинов, костных морфогенных белков, процессы дифференциации преостеобластов и остеобластов, синтетическая функция остеобластов и значение остеобластов в регуляции функции остеокластов.

In the first part of the review, we discussed questions of bone tissue structural organization, Wnt-proteins function, bone morphogenic proteins, preosteoblast to osteoblast differentiation processes, synthetic function of osteoblasts and osteoblast importance in the regulation of osteoclast function.

костные морфогенные белкиостеобластыостеокластыхроническая болезнь почекWnt-протеиныWnt-proteinsbone morphogenic proteinsosteoblastsosteoclastschronic kidney diseaseReferencesClarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 2008; 3 Suppl 3: S131-139Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 2008; 3 Suppl 3: S131-139Quarles L.D. Endocrine functions of bone in mineral metabolism regulation. J Clin Invest. 2008; 118(12): 3820-3828Quarles L.D. Endocrine functions of bone in mineral metabolism regulation. J Clin Invest. 2008; 118(12): 3820-3828Fukumato S., Martin T.J. Bone as an endocrine organ. Trends Endocrinol Metab. 2009; 20(5): 230-236Fukumato S., Martin T.J. Bone as an endocrine organ. Trends Endocrinol Metab. 2009; 20(5): 230-236Хэм А., Кормак Д. Гистология. Т. 1 М.: Мир, 1982; 1360Хэм А., Кормак Д. Гистология. Т. 1 М.: Мир, 1982; 1360Ревелл П.А. Патология кости. М.: Медицина, 1993; 368Ревелл П.А. Патология кости. М.: Медицина, 1993; 368Manolagas S.C. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000; 21(2): 115-137Manolagas S.C. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000; 21(2): 115-137Krishnan V., Bryant H.U., Macdougald O.A. Regulation of bone mass by Wnt signaling. J Clin Invest. 2006; 116(5): 1202-1209.Krishnan V., Bryant H.U., Macdougald O.A. Regulation of bone mass by Wnt signaling. J Clin Invest. 2006; 116(5): 1202-1209.Liu F., Kohlmeier S., Wang C.Y. Wnt signaling and skeletal development. Cell Signal. 2008; 20(6): 999-1009Liu F., Kohlmeier S., Wang C.Y. Wnt signaling and skeletal development. Cell Signal. 2008; 20(6): 999-1009Caetano-Lopes J., Canhăo H., Fonseca J.E. Osteoblasts and bone formation. Acta Reumatol Port. 2007; 32(2): 103-110Caetano-Lopes J., Canhăo H., Fonseca J.E. Osteoblasts and bone formation. Acta Reumatol Port. 2007; 32(2): 103-110Westendorf J.J., Kahler R.A., Schroeder T.M. Wnt signaling: in osteoblasts and bone diseases. Gene. 2004; 341: 19-39Westendorf J.J., Kahler R.A., Schroeder T.M. Wnt signaling: in osteoblasts and bone diseases. Gene. 2004; 341: 19-39Cadigan K.M., Liu Y.I. Wnt signaling: complexity at the surface. J Cell Sci. 2006; 119(Pt 3): 395-402Cadigan K.M., Liu Y.I. Wnt signaling: complexity at the surface. J Cell Sci. 2006; 119(Pt 3): 395-402Stains J.P., Civitelli R. Genomic approaches to identifying transcriptional regulators of osteoblast differentiation. Genone Biol. 2003; 4(7): 222Stains J.P., Civitelli R. Genomic approaches to identifying transcriptional regulators of osteoblast differentiation. Genone Biol. 2003; 4(7): 222Krane S.M. Identifying genes that regulate bone remodeling as potential therapeutic targets. J Exp Med. 2005: 201(6): 841-843Krane S.M. Identifying genes that regulate bone remodeling as potential therapeutic targets. J Exp Med. 2005: 201(6): 841-843Harada S., Rodan G.A. Control of osteoblast function and regulation of bone mass. Nature. 2003; 423(6937): 349-355Harada S., Rodan G.A. Control of osteoblast function and regulation of bone mass. Nature. 2003; 423(6937): 349-355Ducy P, Schinke T., Karsenty G. The osteoblast: a sophisticated fibroblast under central surveillance. Science. 2000; 289(5484): 1501-4Ducy P, Schinke T., Karsenty G. The osteoblast: a sophisticated fibroblast under central surveillance. Science. 2000; 289(5484): 1501-4Mackie E.J. Osteoblasts: novel roles in orchestration of skeletal architecture. Int J Biochem Cell Biol. 2003; 35(9): 1301-1305Mackie E.J. Osteoblasts: novel roles in orchestration of skeletal architecture. Int J Biochem Cell Biol. 2003; 35(9): 1301-1305Mundios S., Otto F., Mundios C. et al. Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell. 89(5): 773-779Mundios S., Otto F., Mundios C. et al. Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell. 89(5): 773-779Karsenty G. Minireview: transcriptional control of osteoblast differentiation. Endocrinology 2001; 142(7): 2731-2733Karsenty G. Minireview: transcriptional control of osteoblast differentiation. Endocrinology 2001; 142(7): 2731-2733Koga T., Inui M., Inoue K. et al. Costimulatory signal mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature. 2004; 428(6984): 758-763Koga T., Inui M., Inoue K. et al. Costimulatory signal mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature. 2004; 428(6984): 758-763Смирнов А.В. Лечение гломерулопатий циклоспорином: правильный подход с неверным обоснованием. Нефрология. 2010; 14: 9-22Смирнов А.В. Лечение гломерулопатий циклоспорином: правильный подход с неверным обоснованием. Нефрология. 2010; 14: 9-22Day T.F. Guo X., Garrett-Beal L., Yang Y. Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell. 2005; 8(5): 739-750Day T.F. Guo X., Garrett-Beal L., Yang Y. Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell. 2005; 8(5): 739-750Boyden L.M., Mao J., Belsky J. et al. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002; 346(20): 1513-1521Boyden L.M., Mao J., Belsky J. et al. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002; 346(20): 1513-1521Little R.D., Carulli J.P., Del Mastro R.G. et al. A mutation in the LDL-receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet. 2002; 70(1): 11-19Little R.D., Carulli J.P., Del Mastro R.G. et al. A mutation in the LDL-receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet. 2002; 70(1): 11-19Issack P.S., Helfet D.L., Lane J.M. Role of Wnt signaling in bone remodeling and repair. HSS J. 2008; 4(1): 66-70Issack P.S., Helfet D.L., Lane J.M. Role of Wnt signaling in bone remodeling and repair. HSS J. 2008; 4(1): 66-70Winkler D.G., Sutherland M.K., Geoghegan J.C. et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003; 22(23): 6267-6276Winkler D.G., Sutherland M.K., Geoghegan J.C. et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003; 22(23): 6267-6276ten Dijke P., Krause C., de Gorter D.J. et al. Osteocyte-derived sclerostin inhibits bone formation: ist role in bone morphogenetic protein and Wnt signaling. J Bone Joint Surg Am. 2008; 90 Suppl 1: 31-35ten Dijke P., Krause C., de Gorter D.J. et al. Osteocyte-derived sclerostin inhibits bone formation: ist role in bone morphogenetic protein and Wnt signaling. J Bone Joint Surg Am. 2008; 90 Suppl 1: 31-35Li J., Sarosi I., Cattley R.C. et al. Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone. 2006; 39(4): 754-766Li J., Sarosi I., Cattley R.C. et al. Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone. 2006; 39(4): 754-766Qiang Y.W., Barlogie B., Rudikoff S., Shaughnessy J.D. Jr. Dkk1-induced inhibition of Wnt signaling in osteoblast differentiation is an underlying mechanism of bone loss in multiple myeloma. Bone. 2008; 42(4): 669-680Qiang Y.W., Barlogie B., Rudikoff S., Shaughnessy J.D. Jr. Dkk1-induced inhibition of Wnt signaling in osteoblast differentiation is an underlying mechanism of bone loss in multiple myeloma. Bone. 2008; 42(4): 669-680Urist M.R. Bone: formation by autoinduction. Science. 1965; 150(698): 893-899Urist M.R. Bone: formation by autoinduction. Science. 1965; 150(698): 893-899Chen D., Zhao M., Mundy G.R. Bone morphogenetic proteins. Growth Factors. 2004; 22(4): 233-241Chen D., Zhao M., Mundy G.R. Bone morphogenetic proteins. Growth Factors. 2004; 22(4): 233-241Cao X., Chen D. The BMP signaling and vivo bone formation. Gene. 2005; 357(1): 1-8Cao X., Chen D. The BMP signaling and vivo bone formation. Gene. 2005; 357(1): 1-8Otsuka F. Multiple endocrine regulation by bone morphogenetic protein system. Endocr. J. 2010; 57(1): 3-14Otsuka F. Multiple endocrine regulation by bone morphogenetic protein system. Endocr. J. 2010; 57(1): 3-14Otani H., Otsuka F., Inagaki K. et al. Aldosterone breakthrough caused by chronic blockage of angiotensin II type 1 receptors in human adrenocortical cells: possible involvement of bone morphogenetic protein-6 actions. Endocrinology. 2008; 149(6): 2816-2825Otani H., Otsuka F., Inagaki K. et al. Aldosterone breakthrough caused by chronic blockage of angiotensin II type 1 receptors in human adrenocortical cells: possible involvement of bone morphogenetic protein-6 actions. Endocrinology. 2008; 149(6): 2816-2825Otani H., Otsuka F., Inagaki K. et al. Roles of bone morphogenetic protein-6 in aldosterone regulation by adrenocortical cells. Acta Med Okayama. 2010; 64(4): 213-218Otani H., Otsuka F., Inagaki K. et al. Roles of bone morphogenetic protein-6 in aldosterone regulation by adrenocortical cells. Acta Med Okayama. 2010; 64(4): 213-218Goto J., Otsuka F., Yamashita M. et al. Enhancement of aldosterone-induced catecholamine production by bone morphogenetic protein-4 through activating Rho and SAPK/JNK pathway in adrenomedullar cells. Am J Physiol Endocrinol Metab. 2009; 296(4): E904-916Goto J., Otsuka F., Yamashita M. et al. Enhancement of aldosterone-induced catecholamine production by bone morphogenetic protein-4 through activating Rho and SAPK/JNK pathway in adrenomedullar cells. Am J Physiol Endocrinol Metab. 2009; 296(4): E904-916Takeda M., Otsuka F., Nakamura K. et al. Characterization of the bone morphogenetic protein (BMP) system in human pulmonary arterial smooth muscle cells isolated from a sporadic case of primary pulmonary hypertension: roles of BMP type IB receptor (activin receptor-like kinase-6) in the mitotic action. Endocrinology. 2004; 145(9): 4344-4354Takeda M., Otsuka F., Nakamura K. et al. Characterization of the bone morphogenetic protein (BMP) system in human pulmonary arterial smooth muscle cells isolated from a sporadic case of primary pulmonary hypertension: roles of BMP type IB receptor (activin receptor-like kinase-6) in the mitotic action. Endocrinology. 2004; 145(9): 4344-4354Wang S., Chen Q., Simon T.C. et al. Bone morphogenic protein-7 (BMP-7), a novel therapy for diabetic nephropathy. Kidney Int. 2003; 63(6): 2037-2049Wang S., Chen Q., Simon T.C. et al. Bone morphogenic protein-7 (BMP-7), a novel therapy for diabetic nephropathy. Kidney Int. 2003; 63(6): 2037-2049Morrissey J., Hruska K., Guo G. et al. Bone morphogenetic protein-7 improves renal fibrosis and accelerates the return of renal function. J Am Soc Nephrol. 2002; 13 Suppl 1: S14-21Morrissey J., Hruska K., Guo G. et al. Bone morphogenetic protein-7 improves renal fibrosis and accelerates the return of renal function. J Am Soc Nephrol. 2002; 13 Suppl 1: S14-21Abe E., Yamamoto M., Taguchi Y. et al. Essential reguirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: antagonism by noggin. J Bone Miner Res. 2000; 15(4): 663-673Abe E., Yamamoto M., Taguchi Y. et al. Essential reguirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: antagonism by noggin. J Bone Miner Res. 2000; 15(4): 663-673Cheng H., Jiang W., Phillips F.M. et al. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am. 2003; 85-A(8): 1544-1552Cheng H., Jiang W., Phillips F.M. et al. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am. 2003; 85-A(8): 1544-1552Fiedler J., Röderer G., Günther K.P., Brenner R.E. BMP-2, BMP-4 and PDGF-bb stimulate chemotactic migration of primary human mesenchymal progenitor cells. J Cell Biochem. 2002; 87(3): 305-312Fiedler J., Röderer G., Günther K.P., Brenner R.E. BMP-2, BMP-4 and PDGF-bb stimulate chemotactic migration of primary human mesenchymal progenitor cells. J Cell Biochem. 2002; 87(3): 305-312Canalis E., Giustina A., Bilezikian J.P. Mechanisms of anabolic therapies for asteoporosis. N Engl J Med. 2007; 357(9): 905-916Canalis E., Giustina A., Bilezikian J.P. Mechanisms of anabolic therapies for asteoporosis. N Engl J Med. 2007; 357(9): 905-916Ducy P., Zhang R., Geoffroy V. et al. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997; 89(5): 747-754Ducy P., Zhang R., Geoffroy V. et al. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997; 89(5): 747-754Sakou T. Bone morphogenetic proteins: from basic studies to clinical approaches. Bone. 1998; 22(6): 591-603Sakou T. Bone morphogenetic proteins: from basic studies to clinical approaches. Bone. 1998; 22(6): 591-603Nordsletten L., Madsen J.E. The effect of bone morphogenetic proteins in fracture healing. Scand J Surg. 2006; 95(2): 91-94Nordsletten L., Madsen J.E. The effect of bone morphogenetic proteins in fracture healing. Scand J Surg. 2006; 95(2): 91-94Herrington J., Carter-Su C. Signaling pathways activated by the growth hormone receptor. Trends Endocrinol Metab. 2001; 12(6): 252-257Herrington J., Carter-Su C. Signaling pathways activated by the growth hormone receptor. Trends Endocrinol Metab. 2001; 12(6): 252-257Canalis E. The fate of circulating osteoblasts. N Engl J Med. 2005; 352(19): 2014-2016Canalis E. The fate of circulating osteoblasts. N Engl J Med. 2005; 352(19): 2014-2016Zhao G., Monier-Faugere M.C., Langub M.C. et al. Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: increased trabecular bone volume without increased osteoblast proliferation. Endocrinology. 2000; 141(7): 2674-2682Zhao G., Monier-Faugere M.C., Langub M.C. et al. Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: increased trabecular bone volume without increased osteoblast proliferation. Endocrinology. 2000; 141(7): 2674-2682Ogata N., Chikazu D., Kubota N. et al. Insulin receptor substrate-1 in osteoblast is indispensable for maintaining bone turnover. J Clin Invest. 2000; 105(7): 935-943Ogata N., Chikazu D., Kubota N. et al. Insulin receptor substrate-1 in osteoblast is indispensable for maintaining bone turnover. J Clin Invest. 2000; 105(7): 935-943Zhang M., Xuan S., Bouxsein M.L. et al. Osteoblast-specific knockout of the insulin- like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. J Biol Chen. 2002; 277(46): 44005-44012Zhang M., Xuan S., Bouxsein M.L. et al. Osteoblast-specific knockout of the insulin- like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. J Biol Chen. 2002; 277(46): 44005-44012Lombardi G., Di Somma C., Vuolo L. et al. Role of IGF-I on PTH effects on bone. J Endocrinol Invest. 2010; 33(7 Suppl): 22-26Lombardi G., Di Somma C., Vuolo L. et al. Role of IGF-I on PTH effects on bone. J Endocrinol Invest. 2010; 33(7 Suppl): 22-26Dobnig H., Turner R.T. Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology. 1995; 136(8): 3632-3638Dobnig H., Turner R.T. Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology. 1995; 136(8): 3632-3638Poole K.E., Reeve J. Parathyroid hormone - a bone anabolic and catabolic agent. Curr Opin Pharmacol. 2005; 5(6): 612-617Poole K.E., Reeve J. Parathyroid hormone - a bone anabolic and catabolic agent. Curr Opin Pharmacol. 2005; 5(6): 612-617Jilka R.L. Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone. 2007; 40(6): 1434-1446Jilka R.L. Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone. 2007; 40(6): 1434-1446Kramer I., Keller H., Leupin O., Kneissel M. Does osteocytic SOST suppression mediate PTH bone anabolism? Trends Endocrinol Metab. 2010; 21(4); 237-244Kramer I., Keller H., Leupin O., Kneissel M. Does osteocytic SOST suppression mediate PTH bone anabolism? Trends Endocrinol Metab. 2010; 21(4); 237-244Schnoke M., Midura S.B., Midura R.J. Parathyroid hormone suppresses osteoblast apoptosis by augmenting DNA repair. Bone.2009; 45(3): 590-602Schnoke M., Midura S.B., Midura R.J. Parathyroid hormone suppresses osteoblast apoptosis by augmenting DNA repair. Bone.2009; 45(3): 590-602Sabbieti M.G., Agas D., Xiao L. et al. Endogenous FGF-2 is critically important in PTH anabolic effects on bone. J Cell Physiol. 2009; 219(1): 143-151Sabbieti M.G., Agas D., Xiao L. et al. Endogenous FGF-2 is critically important in PTH anabolic effects on bone. J Cell Physiol. 2009; 219(1): 143-151Qin L., Tamasi J., Raggatt L. et al. Amphiregulin is a novel growth factor involved in normal bone development and in the cellular response to parathyroid hormone stimulation. J Biol Chem. 2005; 280(5): 3974-3981Qin L., Tamasi J., Raggatt L. et al. Amphiregulin is a novel growth factor involved in normal bone development and in the cellular response to parathyroid hormone stimulation. J Biol Chem. 2005; 280(5): 3974-3981Guo J., Liu M., Yang D. et al. Suppression of Wnt signaling by Dkk1 attenuates PTH-mediated stromal cell response and new bone formation. Cell Metab. 2010; 11(2): 161-171Guo J., Liu M., Yang D. et al. Suppression of Wnt signaling by Dkk1 attenuates PTH-mediated stromal cell response and new bone formation. Cell Metab. 2010; 11(2): 161-171Cejka D., Herberth J., Branscum A.J. et al. Sclerostin and Dickkopf-1 in Renal Osteodystrophy. Clin J Am Nephrol. 2011; 6(4): 877-882Cejka D., Herberth J., Branscum A.J. et al. Sclerostin and Dickkopf-1 in Renal Osteodystrophy. Clin J Am Nephrol. 2011; 6(4): 877-882Yamaguchi M., Ogata N., Shinoda Y et al. Insulin receptor substrate-1 is reguired for bone anabolic function of parathyroid hormone in mice. Endocrinology. 2005; 146(6): 2620-2628Yamaguchi M., Ogata N., Shinoda Y et al. Insulin receptor substrate-1 is reguired for bone anabolic function of parathyroid hormone in mice. Endocrinology. 2005; 146(6): 2620-2628Chen P., Miller P.D., Delmas P.D. et al. Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis. J Bone Miner Res. 2006; 21(11): 1785-1790Chen P., Miller P.D., Delmas P.D. et al. Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis. J Bone Miner Res. 2006; 21(11): 1785-1790Rubin M.R., Bilezikian J.P. The anabolic effects of parathyroid hormone therapy. Clin Geriatr Med. 2003; 19(2): 415-432Rubin M.R., Bilezikian J.P. The anabolic effects of parathyroid hormone therapy. Clin Geriatr Med. 2003; 19(2): 415-432Veis A. Mineral-matrix interactions in bone and dentin. J Bone Miner Res. 1993; 8 Suppl 2: S493-497Veis A. Mineral-matrix interactions in bone and dentin. J Bone Miner Res. 1993; 8 Suppl 2: S493-497Bernards M.T., Qin C., Ratner B.D., Jiang s. Adhesion of MC3T3-E1 cells to bone sialoprotein and bone osteopontin specifically bound to collagen I. J Biomed Mater Res A. 2008; 86(3): 779-787Bernards M.T., Qin C., Ratner B.D., Jiang s. Adhesion of MC3T3-E1 cells to bone sialoprotein and bone osteopontin specifically bound to collagen I. J Biomed Mater Res A. 2008; 86(3): 779-787Seibel M.J. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev. 2005; 26(4): 97-122Seibel M.J. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev. 2005; 26(4): 97-122Chenu C., Colucci S., Grano M. et al. Osteocalcin induces chemotaxis, secretion of matrix proteins, and calcium- mediated intracellular signaling in human osteoclast- like cells. J Cell Biol. 1994; 127(4): 1149-1158Chenu C., Colucci S., Grano M. et al. Osteocalcin induces chemotaxis, secretion of matrix proteins, and calcium- mediated intracellular signaling in human osteoclast- like cells. J Cell Biol. 1994; 127(4): 1149-1158Brown J.P., Delmas P.D., Malaval L. et al. Serum bone Glaprotein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet. 1984; 1(8386): 1091-1093Brown J.P., Delmas P.D., Malaval L. et al. Serum bone Glaprotein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet. 1984; 1(8386): 1091-1093Cloos P.A., Christgau S. Characterization of aged osteocalcin fragments derived from bone resorption. Clin Lab. 2004; 50(9-10): 585-598Cloos P.A., Christgau S. Characterization of aged osteocalcin fragments derived from bone resorption. Clin Lab. 2004; 50(9-10): 585-598Yamada S., Inaba M., Kurajoh M. et al. Utility of serum tartrate-resistant acid phosphatase (TRACP5b) as a bone resorption marker in patients with chronic kidney disease: independence from renal dysfunction. Clin Endocrinol (Oxf). 2008; 69(2): 189-196Yamada S., Inaba M., Kurajoh M. et al. Utility of serum tartrate-resistant acid phosphatase (TRACP5b) as a bone resorption marker in patients with chronic kidney disease: independence from renal dysfunction. Clin Endocrinol (Oxf). 2008; 69(2): 189-196Bacchetta J., Boutroy S., Guebre-Egziabher F. et al. The relationship between adipokines, osteocalcin and bone guality in chronic kidney disease. Nephrol Dial Transplant. 2009; 24(10): 3120-3125Bacchetta J., Boutroy S., Guebre-Egziabher F. et al. The relationship between adipokines, osteocalcin and bone guality in chronic kidney disease. Nephrol Dial Transplant. 2009; 24(10): 3120-3125Kim Y.S., Paik I.Y., Rhie Y.J., Suh S.H. Integrative physiology: defined novel metabolic roles of osteocalcin. J Korean Med Sci. 2010; 25(7): 985-991Kim Y.S., Paik I.Y., Rhie Y.J., Suh S.H. Integrative physiology: defined novel metabolic roles of osteocalcin. J Korean Med Sci. 2010; 25(7): 985-991Ferron M., Hinoi E., Karsenty G., Ducy P. Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA. 2008; 105(13): 5266-5270Ferron M., Hinoi E., Karsenty G., Ducy P. Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA. 2008; 105(13): 5266-5270Singer F.R., Eyre D.R. Using biochemical markers of bone turnover in clinical practice. Cleve Clin J Med.2008; 75(10): 739-750Singer F.R., Eyre D.R. Using biochemical markers of bone turnover in clinical practice. Cleve Clin J Med.2008; 75(10): 739-750Langlois M.R., Delanghe J.R., Kaufman J.M. et al. Posttranslational heterogeneity of bone alkaline phosphatase in metabolic bone disease. Eur J Clin Chem Clin Biochem. 1994; 32(9): 675-680Langlois M.R., Delanghe J.R., Kaufman J.M. et al. Posttranslational heterogeneity of bone alkaline phosphatase in metabolic bone disease. Eur J Clin Chem Clin Biochem. 1994; 32(9): 675-680Orimo H. The mechanism of miniralisation and the role of alkaline phosphatase in health and disease. J Nippon Med Sch. 2010; 77(1): 4-12Orimo H. The mechanism of miniralisation and the role of alkaline phosphatase in health and disease. J Nippon Med Sch. 2010; 77(1): 4-12Baim S., Miller P.D. Assessing the clinical utility of serum CTX in postmenopausal osteoporosis and its use in predicting risk of osteonecrosis of the jaw. J Bone Miner Res. 2009; 24(4): 561-574Baim S., Miller P.D. Assessing the clinical utility of serum CTX in postmenopausal osteoporosis and its use in predicting risk of osteonecrosis of the jaw. J Bone Miner Res. 2009; 24(4): 561-574Robins S.P. Collagen crosslinks in metabolic bone disease. Acta Orthop Scand Suppl. 1995; 266: 171-175Robins S.P. Collagen crosslinks in metabolic bone disease. Acta Orthop Scand Suppl. 1995; 266: 171-175Martin E., Shapiro J.R. Osteogenesis imperfecta: epidemiology and pathophysiology. Curr Osteoporos Rep. 2007; 5(3): 91-97Martin E., Shapiro J.R. Osteogenesis imperfecta: epidemiology and pathophysiology. Curr Osteoporos Rep. 2007; 5(3): 91-97Gal-Moscovici A., Sprague S.M. Role of bone biopsy in stages 3 to 4 chronic kidney disease. Clin J Am Soc Nephrol. 2008; 3 Suppl 3: S170-174Gal-Moscovici A., Sprague S.M. Role of bone biopsy in stages 3 to 4 chronic kidney disease. Clin J Am Soc Nephrol. 2008; 3 Suppl 3: S170-174Goodman W.G. O’Connor J. Aluminum alters calcium influx and efflux from bone in vitro. Kidney Int. 1991; 39(4): 602-607Goodman W.G. O’Connor J. Aluminum alters calcium influx and efflux from bone in vitro. Kidney Int. 1991; 39(4): 602-607Hodgson S.F. Skeletal remodeling and renal osteodystrophy. Semin Nephrol. 1986; 6(1): 42-55Hodgson S.F. Skeletal remodeling and renal osteodystrophy. Semin Nephrol. 1986; 6(1): 42-55Kidd P.M. Vitamins D and K as pleiotropic nutrients: clinical importance to the skeletal and cardiovascular systems and preliminary evidence for synergy. Altern Med Rev. 2010; 15(3): 199-222Kidd P.M. Vitamins D and K as pleiotropic nutrients: clinical importance to the skeletal and cardiovascular systems and preliminary evidence for synergy. Altern Med Rev. 2010; 15(3): 199-222Weiner S., Sagi I., Addadi L. Structular biology. Choosing the crystallization path less traveled. Science. 2005; 309(5737): 1027-1028Weiner S., Sagi I., Addadi L. Structular biology. Choosing the crystallization path less traveled. Science. 2005; 309(5737): 1027-1028Anderson H.C. Matrix vesicles and calcification. Curr Rheumatol Rep.2003; 5(3): 222-226Anderson H.C. Matrix vesicles and calcification. Curr Rheumatol Rep.2003; 5(3): 222-226Boyce B.F., Xing L. Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther. 2007; 9 Suppl 1: S1Boyce B.F., Xing L. Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther. 2007; 9 Suppl 1: S1Lacey D.L., Timms E., Tan H.L. et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998; 93(2): 165-176Lacey D.L., Timms E., Tan H.L. et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998; 93(2): 165-176Onyia J.E., Miles R.R., Yang X. et al. In vivo demonstration that human parathyroid hormone 1-38 inhibits the expression of osteoprotegerin in bone with the kinetics of an immediate early gene. J Bone Miner Res. 2000; 15(5): 863-871Onyia J.E., Miles R.R., Yang X. et al. In vivo demonstration that human parathyroid hormone 1-38 inhibits the expression of osteoprotegerin in bone with the kinetics of an immediate early gene. J Bone Miner Res. 2000; 15(5): 863-871Huang J.C., Sakata T., Pfleger L.L. et al. PTH differentially regulates expression of RANKL and OPG.J Bone Miner Res. 2004; 19(2): 235-244Huang J.C., Sakata T., Pfleger L.L. et al. PTH differentially regulates expression of RANKL and OPG.J Bone Miner Res. 2004; 19(2): 235-244Avbersek-Luznik I., Balon B.P., Rus I., Marc J. Increased bone resorption in HD patients: is it caused by elevated RANKL synthesis. Nephrol Dial Transplant. 2005; 20(3): 566-570Avbersek-Luznik I., Balon B.P., Rus I., Marc J. Increased bone resorption in HD patients: is it caused by elevated RANKL synthesis. Nephrol Dial Transplant. 2005; 20(3): 566-570Coen G., Ballanti P., Balducci A. et al. Serum osteoprotegerin and renal osteodystrophy. Nephrol Dial Transplant. 2002; 17(2): 233-238Coen G., Ballanti P., Balducci A. et al. Serum osteoprotegerin and renal osteodystrophy. Nephrol Dial Transplant. 2002; 17(2): 233-238Moe S.M., Drüeke T. Improving global outcomes in mineral and bone disorders. Clin J Am Soc Nephrol. 2008; 3 Suppl 3: S127-130Moe S.M., Drüeke T. Improving global outcomes in mineral and bone disorders. Clin J Am Soc Nephrol. 2008; 3 Suppl 3: S127-130Couttenye M.M., D’Haese P.C., Verschoren W.J. et al. Low bone turnover in patients with renal failure. Kidney Int Suppl. 1999; 73: S70-76Couttenye M.M., D’Haese P.C., Verschoren W.J. et al. Low bone turnover in patients with renal failure. Kidney Int Suppl. 1999; 73: S70-76Iwasaki- Ishizuka Y., Yamato H., Nii-Kono T. et al. Down-regulation of parathyroid hormone receptor gene expression and osteoblastic dysfunction associated with skeletal resistance to parathyroid hormone in a rat model of renal failure with low turnover bone. Nephrol Dial Transplant. 2005; 20(9): 1904-1911Iwasaki- Ishizuka Y., Yamato H., Nii-Kono T. et al. Down-regulation of parathyroid hormone receptor gene expression and osteoblastic dysfunction associated with skeletal resistance to parathyroid hormone in a rat model of renal failure with low turnover bone. Nephrol Dial Transplant. 2005; 20(9): 1904-1911Picton M.L., Moore P.R., Mawer E.B. et al. Down-regulation of human osteoblast PTH/PTHrP receptor mRNA in end-stage renal failure. Kidney Int. 2000; 58(4): 1440-1449Picton M.L., Moore P.R., Mawer E.B. et al. Down-regulation of human osteoblast PTH/PTHrP receptor mRNA in end-stage renal failure. Kidney Int. 2000; 58(4): 1440-1449Adams J.S., Hewison M. Update in vitamin D. J Clin Endocrinol Metab. 2010: 95(2): 471-478Adams J.S., Hewison M. Update in vitamin D. J Clin Endocrinol Metab. 2010: 95(2): 471-478Malaponte G., Bevelacgua V., Fatuzzo P. et al. IL-1beta, TNF-alpha and IL-6 release from monocytes in haemodialysis patients in relation to dialytic age. Nephrol Dial Transplant. 2002; 17(11): 1964-1970Malaponte G., Bevelacgua V., Fatuzzo P. et al. IL-1beta, TNF-alpha and IL-6 release from monocytes in haemodialysis patients in relation to dialytic age. Nephrol Dial Transplant. 2002; 17(11): 1964-1970Duarte M.E., Carvalho E.F., Cruz E.A. et al. Cytokine accumulation in osteitis fibrosa of renal osteodystrophy. Braz J Med Biol Res. 2002; 35(1): 25-29Duarte M.E., Carvalho E.F., Cruz E.A. et al. Cytokine accumulation in osteitis fibrosa of renal osteodystrophy. Braz J Med Biol Res. 2002; 35(1): 25-29Santos F.R., Moyses R.M., Montenegro F.L. et al. IL-1beta, TNF-alpha, TGF-beta, and bFGF expression in bone biopsies before and after parathyroidectomy. Kidney Int. 2003; 63(3): 899-907Santos F.R., Moyses R.M., Montenegro F.L. et al. IL-1beta, TNF-alpha, TGF-beta, and bFGF expression in bone biopsies before and after parathyroidectomy. Kidney Int. 2003; 63(3): 899-907Greenfield E.M., Shaw S.M., Gornik S.A., Banks M.A. Adenyl cyclase and interleukin 6 are downstream effectors of parathyroid hormone resulting in stimulation of bone resorption. J Clin Invest. 1995; 96(3): 1238-1244Greenfield E.M., Shaw S.M., Gornik S.A., Banks M.A. Adenyl cyclase and interleukin 6 are downstream effectors of parathyroid hormone resulting in stimulation of bone resorption. J Clin Invest. 1995; 96(3): 1238-1244Groopman J.E., Molina J.M., Scadden D.T. Hematopoietic growth factors. Biology and clinical applications. N Engl J Med. 1989; 321(21): 1449-1459Groopman J.E., Molina J.M., Scadden D.T. Hematopoietic growth factors. Biology and clinical applications. N Engl J Med. 1989; 321(21): 1449-1459Schett G., Stach C., Zwerina J. et al. How antirheumatic drugs protect joints from damage in rheumatoid arthritis. Arthritis Rheum. 2008; 58(10): 2936-2948Schett G., Stach C., Zwerina J. et al. How antirheumatic drugs protect joints from damage in rheumatoid arthritis. Arthritis Rheum. 2008; 58(10): 2936-2948Freundlich M., Alonzo E., Bellorin-Font E., Weisinger J.R. Increased osteoblastic activity and expression of receptor activator of NF-kappaB ligand in nonuremic nephrotic syndrome. J Am Soc Nephrol. 2005; 16(7): 2198-2204Freundlich M., Alonzo E., Bellorin-Font E., Weisinger J.R. Increased osteoblastic activity and expression of receptor activator of NF-kappaB ligand in nonuremic nephrotic syndrome. J Am Soc Nephrol. 2005; 16(7): 2198-2204Sweiss N.J., Hushaw L.L. Biologic agents for rheumatoid arthritis: 2008 and beyond. J Infus Nurs. 2009; 32(1 Suppl): S4-17Sweiss N.J., Hushaw L.L. Biologic agents for rheumatoid arthritis: 2008 and beyond. J Infus Nurs. 2009; 32(1 Suppl): S4-17Wada T., Nakashima T., Hiroshi N., Penninger J.M. RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med. 2006; 12(1): 17-25Wada T., Nakashima T., Hiroshi N., Penninger J.M. RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med. 2006; 12(1): 17-25Cummings S.R., San Martin J., McClung M.R. et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009; 361(8): 756-765Cummings S.R., San Martin J., McClung M.R. et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009; 361(8): 756-765Fill S., Karalaki M., Schaller B. Therapeutic implications of osteoprotegerin. Cancer Cell Int. 2009; 9: 26Fill S., Karalaki M., Schaller B. Therapeutic implications of osteoprotegerin. Cancer Cell Int. 2009; 9: 26Гельцер Б.И., Кочеткова Е.А., Семисотова Е.Ф. и др. Атеросклероз и остеопороз: общий взгляд на проблему. Тер. архив. 2006; 78 (10): 81-85Гельцер Б.И., Кочеткова Е.А., Семисотова Е.Ф. и др. Атеросклероз и остеопороз: общий взгляд на проблему. Тер. архив. 2006; 78 (10): 81-85Pritzker L.B., Scatena M., Giachelli C.M. The role of osteoprotegerin and tumor necrosis factor-related apoptosis-inducing ligand in human microvascular endothelial cell survival. Mol Biol Cell. 2004; 15(6): 2834-2841Pritzker L.B., Scatena M., Giachelli C.M. The role of osteoprotegerin and tumor necrosis factor-related apoptosis-inducing ligand in human microvascular endothelial cell survival. Mol Biol Cell. 2004; 15(6): 2834-2841Venuraju S.M., Yerramasu A., Corder R., Lahiri F. Osteoprotegerin as a predictor of coronary artery disease and cardiovascular mortality and morbidity. J Am Coll Cardiol. 2010; 55(19): 2049-2061Venuraju S.M., Yerramasu A., Corder R., Lahiri F. Osteoprotegerin as a predictor of coronary artery disease and cardiovascular mortality and morbidity. J Am Coll Cardiol. 2010; 55(19): 2049-2061Jono S., Ikari Y., Shioi A. et al. Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation. 2002; 106(10): 1192-1194Jono S., Ikari Y., Shioi A. et al. Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation. 2002; 106(10): 1192-1194Kiechl S., Schett G., Wenning G. et al. Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation. 2004; 109(18): 2175-2180Kiechl S., Schett G., Wenning G. et al. Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation. 2004; 109(18): 2175-2180Avignon A., Sultan A., Piot C. et al. Osteoprotegerin: a novel independent marker for silent myocardial ischemia in asymptomatic diabetic patients. Diabetes Care. 2007; 30(11): 2934-2939Avignon A., Sultan A., Piot C. et al. Osteoprotegerin: a novel independent marker for silent myocardial ischemia in asymptomatic diabetic patients. Diabetes Care. 2007; 30(11): 2934-2939Omland T., Ueland T., Jansson A.M. et al. Circulating osteoprotegerin levels and long-term prognosis in patients with acute coronary syndromes. J Am Coll Cardiol. 2008; 51(6): 627-633Omland T., Ueland T., Jansson A.M. et al. Circulating osteoprotegerin levels and long-term prognosis in patients with acute coronary syndromes. J Am Coll Cardiol. 2008; 51(6): 627-633Morena M., Terrier N., Jaussent I. et al. Plasma osteoprotegerin is associated with mortality in hemodialysis patients. J Am Soc Nephrol. 2006; 17(1): 262-270Morena M., Terrier N., Jaussent I. et al. Plasma osteoprotegerin is associated with mortality in hemodialysis patients. J Am Soc Nephrol. 2006; 17(1): 262-270Hjelmesaeth J., Ueland T., Flyvbjerg A. et al. Early posttransplant serum osteoprotegerin levels predict long-term (8-year) patient survival and cardiovascular death in renal transplant patients. J Am Soc Nephrol. 2006; 17(6): 1746-1754Hjelmesaeth J., Ueland T., Flyvbjerg A. et al. Early posttransplant serum osteoprotegerin levels predict long-term (8-year) patient survival and cardiovascular death in renal transplant patients. J Am Soc Nephrol. 2006; 17(6): 1746-1754Sigrist M.K., Levin A., Er L., Mclntyre C.W. Elevated osteoprotegerin is associated with all-cause mortality in CKD stage and 5 patients in addition to vascular calcification. Nephrol Dial Transplant. 2009; 24(10): 3157-3162Sigrist M.K., Levin A., Er L., Mclntyre C.W. Elevated osteoprotegerin is associated with all-cause mortality in CKD stage and 5 patients in addition to vascular calcification. Nephrol Dial Transplant. 2009; 24(10): 3157-3162Bennett B.J., Scatena M., Kirk E.A. et al. Osteoprotegerin inactivation accelerates advanced atherosclerotic lesion progression and calcification in older ApoE-/- mice. Arterioscler Thromb Vasc Biol. 2006; 26(9): 2117-2124Bennett B.J., Scatena M., Kirk E.A. et al. Osteoprotegerin inactivation accelerates advanced atherosclerotic lesion progression and calcification in older ApoE-/- mice. Arterioscler Thromb Vasc Biol. 2006; 26(9): 2117-2124Jono S., Ikari Y., Shioi A. et al. Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation. 2002; 106(10): 1192-1194Jono S., Ikari Y., Shioi A. et al. Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation. 2002; 106(10): 1192-1194Anand D.V., Lahiri A., Lim E. et al. The relationship between plasma osteoprotegerin levels and coronary artery calcification in uncomplicated type 2 diabetic subjects. J Am Coll Cardiol. 2006; 47(9): 1850-1857Anand D.V., Lahiri A., Lim E. et al. The relationship between plasma osteoprotegerin levels and coronary artery calcification in uncomplicated type 2 diabetic subjects. J Am Coll Cardiol. 2006; 47(9): 1850-1857Nitta K., Akiba T., Uchida K. et al. Serum osteoprotegerin levels and the extent of vascular calcification in haemodialysis patients. Nephrol Dial Transplant. 2004; 19(7): 1886-1889Nitta K., Akiba T., Uchida K. et al. Serum osteoprotegerin levels and the extent of vascular calcification in haemodialysis patients. Nephrol Dial Transplant. 2004; 19(7): 1886-1889Morena M., Dupuy A.M., Jaussent I. et al. A cut-off value of plasma osteoprotegerin level may predict the presence of coronary artery calcifications in chronic kidney disease patients. Nephrol Dial Transplant. 2009; 24(11): 3389-3397Morena M., Dupuy A.M., Jaussent I. et al. A cut-off value of plasma osteoprotegerin level may predict the presence of coronary artery calcifications in chronic kidney disease patients. Nephrol Dial Transplant. 2009; 24(11): 3389-3397

The authors declare that there are no conflicts of interest present.