[1] Van Hul W, Balemans W, Van Hul E, Dikkers FG, Obee H, Stokroos RJ, Hildering P, Vanhoenacker F, Van Camp G, Willems PJ. Van Buchem disease (hyperostosis corticalis generalisata) maps to chromosome 17q12-q21. Am J Hum Genet, 1998, 62(2): 391-399.

[2] Balemans W, Van Den Ende J, Paes-Alves AF, Dikkers FG, Willems PJ, Vanhoenacker F, de Almeida-Melo N, Alves CF, Stratakis CA, Hill SC, Van Hul W. Localization of the gene for sclerosteosis to the van Buchem disease-gene re-gion on chromosome 17q12-q21. Am J Hum Genet, 1999, 64(6): 1661-1669.

[3] Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den Ende J, Willems P, Paes-Alves AF, Hill S, Bueno M, Ramos FJ, Tacconi P, Dikkers FG, Stratakis C, Lindpaintner K, Vickery B, Fo-ernzler D, Van Hul W. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet, 2001, 10(5): 537-543.

[4] Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo PJ, Fu YH, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan J. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet, 2001, 68(3): 577-589.

[5] Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Löwik CW, Reeve J. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J, 2005, 19(13): 1842-1844.

[6] Mayor C, Brudno M, Schwartz JR, Poliakov A, Rubin EM, Frazer KA, Pachter LS, Dubchak I. VISTA: visualizing global DNA sequence alignments of arbitrary length. Bio-informatics, 2000, 16(11): 1046-1047.

[7] Balemans W, Van Hul W. Human genetics of SOST. J Musculoskelet Neuronal Interact, 2006, 6(4): 355-356.

[8] Pearce JJ, Penny G, Rossant J. A mouse cerberus/Dan-related gene family. Dev Biol, 1999, 209(1): 98-110.

[9] Hsu DR, Economides AN, Wang XR, Eimon PM, Harland RM. The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP ac-tivities. Mol Cell, 1998, 1(5): 673-683.

[10] Veverka V, Henry AJ, Slocombe PM, Ventom A, Mulloy B, Muskett EW, Muzylak M, Greenslade K, Moore A, Zhang L, Gong JH, Qian XM, Paszty C, Taylor RJ, Robinson MK, Carr MD. Characterization of the structural features and interactions of sclerostin: molecular insight into a key regulator of Wnt-mediated bone formation. J Biol Chem, 2009, 284(16): 10890-10900.

[11] Weidauer SE, Schmieder P, Beerbaum M, Beerbaum M, Schmitz W, Oschkinat H, Mueller TD. NMR structure of the Wnt modulator protein sclerostin. Biochem Biophys Res Commun, 2009, 380(1): 160-165.

[12] Loots GG. Kneissel M, Keller H, Baptist M, Chang J, Collette NM, Ovcharenko D, Plajzer-Frick I, Rubin EM. Genomic deletion of a long-range bone enhancer mis-regulates sclerostin in Van Buchem disease. Genome Res, 2005, 15(7): 928-935.

[13] Li X, Ominsky MS, Niu QT, Sun N, Daugherty B, D'Agostin D, Kurahara C, Gao Y, Cao J, Gong J, Asuncion F, Barrero M, Warmington K, Dwyer D, Stolina M, Morony S, Sarosi I, Kostenuik PJ, Lacey DL, Simonet WS, Ke HZ, Paszty C. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res, 2008, 23(6): 860-869.

[14] Li X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, Gao Y, Shalhoub V, Tipton B, Haldankar R, Chen Q, Winters A, Boone T, Geng Z, Niu QT, Ke HZ, Kostenuik PJ, Simonet WS, Lacey DL, Paszty C. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res, 2009, 24(4): 578-588.

[15] Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, Gong J, Gao Y, Cao J, Graham K, Tipton B, Cai J, Deshpande R, Zhou L, Hale MD, Lightwood DJ, Henry AJ, Popplewell AG, Moore AR, Robinson MK, Lacey DL, Simonet WS, Paszty C. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res, 2010, 25(5): 948-959.

[16] Li CY, Ominsky MS, Tan HL, Barrero M, Niu QT, Asuncion FJ, Lee E, Liu M, Simonet WS, Paszty C, Ke HZ. Increased callus mass and enhanced strength during fracture healing in mice lacking the sclerostin gene. Bone, 2011, 49(6): 1178-1185.

[17] Naka T, Yokose S. Spatiotemporal expression of sclerostin in odontoblasts during embryonic mouse tooth morpho-genesis. J Endod, 2011, 37(3): 340-345.

[18] van Bezooijen RL, ten Dijke P, Papapoulos SE, Löwik CWGM. SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev, 2005, 16(3): 319-327.

[19] Keller H, Kneissel M. SOST is a target gene for PTH in bone. Bone, 2005, 37(2): 148-158.

[20] Qin L, Qiu P, Wang LQ, Li X, Swarthout JT, Soteropoulos P, Tolias P, Partridge NC. Gene expression profiles and transcription factors involved in parathyroid hormone signaling in osteoblasts revealed by microarray and bio-informatics. J Biol Chem, 2003, 278(22): 19723-19731.

[21] Sevetson B, Taylor S, Pan Y. Cbfa1/RUNX2 directs specific expression of the sclerosteosis gene (SOST). J Biol Chem, 2004, 279(14): 13849-13858.

[22] Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O'Brien CA, Manolagas SC, Jilka RL. Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by os-teocytes: a novel mechanism for hormonal control of os-teoblastogenesis. Endocrinology, 2005, 146(11): 4577-4583.

[23] Silvestrini G, Ballanti P, Leopizzi M, Sebastiani M, Berni S, Di Vito M, Bonucci E. Effects of intermittent parathy-roid hormone (PTH) administration on SOST mRNA and protein in rat bone. J Mol Histol, 2007, 38(4): 261-269.

[24] Leupin O, Kramer I, Kramer I, Collette NM, Loots GG, Natt F, Kneissel M, Keller H. Control of the SOST bone enhancer by PTH using MEF2 transcription factors. J Bone Miner Res, 2007, 22(12): 1957-1967.

[25] Huang QY, Li GH, Kung AWC. The -9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPα and FOXA1 binding is associated with osteoporosis. Bone, 2009, 45(2): 289-294.

[26] 赵薇, 王志军, 丁娟, 吕金捍. 绝经后骨质疏松妇女血清骨硬化蛋白与雌二醇的相关性分析. 现代生物医学进展, 2010, 10(23): 4488-4490.

[27] Yang F, Tang WJ, So S, de Crombrugghe B, Zhang C. Sclerostin is a direct target of osteoblast-specific tran-scription factor osterix. Biochem Biophys Res Commun, 2010, 400(4): 684-688.

[28] Loots GG, Keller H, Leupin O, Murugesh D, Collette NM, Genetos DC. TGF-β regulates sclerostin expression via the ECR5 enhancer. Bone, 2012, 50(3): 663-669.

[29] Kramer I, Baertschi S, Halleux C, Keller H, Kneissel M. Mef2c deletion in osteocytes results in increased bone mass. J Bone Miner Res, 2012, 27(2): 360-373.

[30] Collette NM, Genetos DC, Economides AN, Xie L, Shahnazari M, Yao W, Lane NE, Harland RM, Loots GG. Targeted deletion of Sost distal enhancer increases bone formation and bone mass. Proc Natl Acad Sci USA, 2012, 109(35): 14092-14097.

[31] Cohen-Kfir E, Artsi H, Levin A, Abramowitz E, Bajayo A, Gurt I, Zhong L, D'Urso A, Toiber D, Mostoslavsky R, Dresner-Pollak R, Mostoslavsky R, Dresner-Pollak R. Sirt1 is a regulator of bone mass and a repressor of sost encoding for sclerostin: a bone formation inhibitor. Endo-crinology, 2011, 152(12): 4514-4524.

[32] Kaneko K, Ito M, Fumoto T, Fukuhara R, Ishida J, Fukamizu A, Ikeda K. Physiological function of the an-giotensin AT1a receptor in bone remodeling. J Bone Miner Res, 2011, 26(12): 2959-2966.

[33] Kim BJ, Bae SJ, Lee SY, Lee YS, Baek JE, Park SY, Lee SH, Koh JM, Kim GS. TNF-α mediates the stimulation of sclerostin expression in an estrogen-deficient condition. Biochem Biophys Res Commun, 2012, 424(1): 170-175.

[34] Tu XL, Rhee Y, Condon KW, Bivi N, Allen MR, Dwyer D, Stolina M, Turner CH, Robling AG, Plotkin LI, Bellido T. Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading. Bone, 2012, 50(1): 209-217.

[35] Genetos DC, Toupadakis CA, Raheja LF, Wong A, Papanicolaou SE, Fyhrie DP, Loots GG, Yellowley CE. Hypoxia decreases sclerostin expression and increases Wnt signaling in osteoblast. J Cell Biochem, 2010, 110(2): 457-467.

[36] Delgado-Calle J, Sañudo C, Bolado A, Fernández AF, Arozamena J, Pascual-Carra MA, Rodriguez-Rey JC, Fraga MF, Bonewald L, Riancho JA. DNA methylation contributes to the regulation of sclerostin expression in human osteocytes. J Bone Miner Res, 2012, 27(4): 926-937.

[37] Hassan MQ, Maeda Y, Taipaleenmaki H, Zhang WB, Jafferji M, Gordon JA, Li ZY, Croce CM, van Wijnen AJ, Stein JL, Stein GS, Lian JB. miR-218 Directs a Wnt sig-naling circuit to promote differentiation of osteoblasts and osteomimicry of metastatic cancer cells. J Biol Chem, 2012, 287(50): 42084-42092.

[38] Balemans W, Cleiren E, Siebers U, Horst J, Van Hul W. A generalized skeletal hyperostosis in two siblings caused by a novel mutation in the SOST gene. Bone, 2005, 36(6): 943-947.

[39] Kim SJ, Bieganski T, Sohn YB, Kozlowski K, Semënov M, Okamoto N, Kim CH, Ko AR, Ahn GH, Choi YL, Park SW, Ki CS, Kim OH, Nishimura G, Unger S, Superti-Furga A, Jin DK. Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dys-plasia. Hum Genet, 2011, 129(5): 497-502.

[40] Huang QY, Kung AWC. Genetics of osteoporosis. Mol Genet Metab, 2006, 88(4): 295-306.

[41] Uitterlinden AG, Arp PP, Paeper BW, Charmley P, Proll S, Rivadeneira F, Fang Y, van Meurs JB, Britschgi TB, Latham JA, Schatzman RC, Pols HA, Brunkow ME. Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites. Am J Hum Genet, 2004, 75(6): 1032-1045.

[42] Valero C, Zarrabeitia MT, Hernández JL, Pineda B, Cano A, García-Pérez MA, Riancho JA. Relationship of scle-rostin and secreted frizzled protein polymorphisms with bone mineral density: an association study with replication in postmenopausal women. Menopause, 2011, 18(7): 802-807.

[43] Piters E, de Freitas F, Nielsen TL, Andersen M, Brixen K, Van Hul W. Association study of polymorphisms in the SOST gene region and parameters of bone strength and body composition in both young and elderly men: data from the Odense Androgen Study. Calcif Tissue Int, 2012, 90(1): 30-39.

[44] Yerges LM, Klei L, Cauley JA, Roeder K, Kammerer CM, Moffett SP, Ensrud KE, Nestlerode CS, Marshall LM, Hoffman AR, Lewis C, Lang TF, Barrett-Connor E, Ferrell RE, Orwoll ES, Zmuda JM; MrOS Research Group. High- density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men. J Bone Miner Res, 2009, 24(12): 2039-2049.

[45] Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, Jonsdottir T, Saemundsdottir J, Snorradóttir S, Center JR, Nguyen TV, Alexandersen P, Gulcher JR, Eisman JA, Christiansen C, Sigurdsson G, Kong A, Thorsteinsdottir U, Stefansson K. New sequence variants associated with bone mineral den-sity. Nat Genet, 2009, 41(1): 15-17.

[46] Krishnan V, Bryant HU. Macdougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest, 2006, 116(5): 1202-1209.

[47] Bodine PV, Komm BS. Wnt signaling and osteoblasto-genesis. Rev Endocr Metab Disord, 2006, 7(1-2): 33-39.

[48] Kamiya N. The Role of BMPs in bone anabolism and their potential targets SOST and DKK1. Curr Mol Pharmacol, 2012, 5(2): 153-163.

[49] Bourhis E, Wang WR, Tam C, Hwang J, Zhang YN, Spittler D, Huang OW, Gong Y, Estevez A, Zilberleyb I, Rouge L, Chiu C, Wu Y, Costa M, Hannoush RN, Franke Y, Cochran AG. Wnt antagonists bind through a short peptide to the first β-propeller domain of LRP5/6. Structure, 2011, 19(10): 1433-1442.

[50] 韩金祥. 骨分子生物学. 北京: 科学出版社, 2010: 222-228.

[51] Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, Appleby M, Brunkow ME, Latham JA. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J, 2003, 22(23): 6267-6276.

[52] Kamiya N, Kaartinen VM, Mishina Y. Loss-of-function of ACVR1 in osteoblasts increases bone mass and activates canonical Wnt signaling through suppression of Wnt in-hibitors SOST and DKK1. Biochem Biophys Res Commun, 2011, 414(2): 326-330.

[53] Krause C, Korchynskyi O, de Rooij K, Weidauer SE, de Gorter DJ, van Bezooijen RL, Hatsell S, Economides AN, Mueller TD, Löwik CW, ten Dijke P. Distinct modes of inhibition by sclerostin on bone morphogenetic protein and Wnt signaling pathways. J Biol Chem, 2010, 285(53): 41614-41626.

[54] Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duode-num. Cell, 2008, 135(5): 825-837.

[55] Vincent C, Findlay DM, Welldon KJ, Wijenayaka AR, Zheng TS, Haynes DR, Fazzalari NL, Evdokiou A, Atkins GJ. Pro-inflammatory cytokines TNF-related weak in-ducer of apoptosis (TWEAK) and TNFα induce the mito-gen-activated protein kinase (MAPK)-dependent expression of sclerostin in human osteoblasts. J Bone Miner Res, 2009, 24(8): 1434-1449.

[56] Choi HY, Dieckmann M, Herz J, Niemeier A. Lrp4, a novel receptor for Dickkopf 1 and sclerostin, is expressed by osteoblasts and regulates bone growth and turnover in vivo. PLoS One, 2009, 4(11): e7930.

[57] Genetos DC, Yellowley CE, Loots GG. Prostaglandin E2 signals through PTGER2 to regulate sclerostin expression. PLoS One, 2011, 6(3): e17772.

[58] Galea GL, Sunters A, Meakin LB, Zaman G, Sugiyama T, Lanyon LE, Price JS. Sost down-regulation by mechanical strain in human osteoblastic cells involves PGE2 signaling via EP4. FEBS Lett, 2011, 585(15): 2450-2454.

[59] Ke HZ, Richards WG, Li XD, Ominsky MS. Sclerostin and dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev, 2012, 33(5): 747-783.

[60] Tian XY, Jee WS, Li XD, Paszty C, Ke HZ. Sclerostin an-tibody increases bone mass by stimulating bone formation and inhibiting bone resorption in a hindlimb-immobilization rat model. Bone, 2011, 48(2): 197-201.

[61] Li X, Warmington KS, Niu QT, Asuncion FJ, Barrero M, Grisanti M, Dwyer D, Stouch B, Thway TM, Stolina M, Ominsky MS, Kostenuik PJ, Simonet WS, Paszty C, Ke HZ. Inhibition of sclerostin by monoclonal antibody in-creases bone formation, bone mass, and bone strength in aged male rats. J Bone Miner Res, 2010, 25(12): 2647-2656.

[62] Okazaki R. Anti-sclerostin antibodies. Clin Calcium, 2011, 21(1): 94-98.

[63] Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. Bone Miner Res, 2011, 26(1): 19-26.