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Current Osteoporosis Reports

Erschienen in:

01.03.2014 | Skeletal Biology and Regulation (MR Forwood and A Robling, Section Editors)

Developments in Sclerostin Biology: Regulation of Gene Expression, Mechanisms of Action, and Physiological Functions

verfasst von: Megan M. Weivoda, Merry Jo Oursler

Erschienen in: Current Osteoporosis Reports | Ausgabe 1/2014

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Abstract

The SOST gene, which encodes the protein sclerostin, was identified through genetic linkage analysis of sclerosteosis and van Buchem’s disease patients. Sclerostin is a secreted glycoprotein that binds to the low-density lipoprotein receptor-related proteins 4, 5, and 6 to inhibit Wnt signaling. Since the initial discovery of sclerostin, much understanding has been gained into the role of this protein in the regulation of skeletal biology. In this article, we discuss the latest findings in the regulation of SOST expression, sclerostin mechanisms of action, and the potential utility of targeting sclerostin in conditions of low bone mass.

van Bezooijen R, ten Dijke P, Papapoulos SE, Lowik CW. SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev. 2005;16:319–27.

van Hul W, Balemans W, van Hul E, Dikkers F, Obee H, Stokroos R, et al. van Buchem Disease (hyperostosis corticalis generalisata) maps to the chromosome 17q12-q21. Am J Hum Genet. 1998;62:391–9.PubMedCentralPubMedCrossRef

Balemans W, Van Den Ende J, Freire Paes-Alves A, Dikkers FG, Willems PJ, Vanhoenacker F, et al. Localization of the Gene for Sclerosteosis to the van Buchem Disease-Gene Region on Chromosome 17q12-q21. Am J Hum Genet. 1999;64:1661–9.

Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Molec Genet. 2001;10(5):537–43.PubMedCrossRef

Brunkow M, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001;68:577–89.PubMedCentralPubMedCrossRef

6.•

van Lierop A, Hamdy NAT, Hamersma H, van Bezooijen RL, Power J, Loveridge N, et al. Patients with sclerosteosis and disease carriers: human models of the effect of sclerostin on bone turnover. J Bone Miner Res. 2011;26(12):2804–11. This manuscript provides evidence that decreased or absent sclerostin leads to increased bone mass in humans. Importantly, decreased sclerostin in sclerosteosis carriers correlated with increased bone mass without disease symptoms.PubMedCrossRef

Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C, et al. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet. 2002;39:91–7.PubMedCrossRef

8.•

van Lierop A, Hamdy NAT, van Egmond ME, Bakker E, Dikkers FG, Papapoulos SE. Van Buchem Disease: clinical, biochemical, and densitometric features of patients and disease carriers. J Bone Miner Res. 2013;28(4):848–54. This manuscript provides evidence that there is a gene-dose effect of the VBD mutation on circulating sclerostin, suggesting that altered sclerostin levels affects the severity of the bone phenotype in VBD and sclerosteosis patients.PubMedCrossRef

Burgers T, Williams BO. Regulation of Wnt/ß-catenin signaling within and from osteocytes. Bone. 2013;54:244–9.PubMedCrossRef

10.

Rossini M, Gatti D, Adami S. Involvement of WNT/ß-catenin Signaling in the treatment of osteoporosis. Calcif Tissue Int. 2013;93:121–32.PubMedCrossRef

11.

Little R, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, 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;70:11–9.PubMedCentralPubMedCrossRef

12.

Boyden L, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, et al. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002;346:1513–21.PubMedCrossRef

13.

Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, et al. LDL Receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001;107(4):513–23. doi:10.1016/S0092-8674(01)00571-2.PubMedCrossRef

14.

Ott S. Editorial: sclerostin and Wnt signaling—the pathway to bone strength. J Clin Endo Metab. 2005;90(12):6741–3.CrossRef

15.

Ohyama Y, Nifuji A, Maeda Y, Amagasa T, Noda M. Spaciotemporal association and bone morphogenetic protein regulation of sclerostin and osterix expression during embryonic osteogenesis. Endocrinology. 2004;145(10):4685–92. doi:10.1210/en.2003-1492.PubMedCrossRef

16.

van Bezooijen RL, Roelen BA, Visser A, van der Wee-Pals L, de Wilt E, Karperien M, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 2004;199(6):805–14. doi:10.1084/jem.20031454.PubMedCentralPubMedCrossRef

17.

Van Bezooijen R, Bronckers A, Gortzak R, Hogendoorn P, van der Wee-Pals L, Balemans W, et al. Sclerostin in mineralized matrices and van Buchem disease. J Dental Res. 2009;88(6):569–74.CrossRef

18.

Moester M, Papapoulos SE, Lowik CWGM, van Bezooijen RL. Sclerostin: current knowledge and future perspectives. Calcif Tissue Int. 2010;87:99–107.PubMedCentralPubMedCrossRef

19.

Kusu N, Laurikkala J, Imanishi M, Usui H, Konishi M, Miyake A, et al. Sclerostin is a novel secreted osteoclast-derived bone morphogenetic protein antagonist with unique ligand specificity. J Biol Chem. 2003;278(26):24113–7. doi:10.1074/jbc.M301716200.PubMedCrossRef

20.

Pederson L, Ruan M, Westendorf JJ, Khosla S, Oursler MJ. Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. Proc Natl Acad Sci U S A. 2008;105(52):20764–9. doi:10.1073/pnas.0805133106.PubMedCentralPubMedCrossRef

21.

Ota K, Quint P, Ruan M, Pederson L, Westendorf JJ, Khosla S, et al. Sclerostin is expressed in osteoclasts from aged mice and reduces osteoclast-mediated stimulation of mineralization. J Cell Biochem. 2013;114(8):1901–7. doi:10.1002/jcb.24537.PubMedCrossRef

22.

Tang W, Li Y, Osimiri L, Zhang C. Osteoblast-specific Transcription Factor Osterix (Osx) is an upstream regulator of Satb2 during bone formation. J Biol Chem. 2011;286(38):32995–3002. doi:10.1074/jbc.M111.244236.PubMedCrossRef

23.

Sevetson B, Taylor S, Pan Y. Cbfa1/RUNX2 directs specific expression of the sclerosteosis gene (SOST). J Biol Chem. 2004;279(14):13849–58. doi:10.1074/jbc.M306249200.PubMedCrossRef

24.

Yang F, Tang W, So S, de Crombrugghe B, Zhang C. Sclerostin is a direct target of osteoblast-specific transcription factor osterix. Biochem Biophys Res Commun. 2010;400(4):684–8. doi:10.1016/j.bbrc.2010.08.128.PubMedCrossRef

25.•

Delgado-Calle J, Sanudo C, Bolado A, Fernandez AF, Arozamena J, Pascual-Carra MA, et al. DNA methylation contributes to the regulation of sclerostin expression in human osteocytes. J Bone Min Res. 2012;27(4):926–37. doi:10.1002/jbmr.1491. These data show that epigenetics contributes to the regulation of sclerostin expression.CrossRef

26.••

Delgado-Calle J, Arozamena J, Perez-Lopez J, Bolado-Carrancio A, Sanudo C, Agudo G, et al. Role of BMPs in the regulation of sclerostin as revealed by an epigenetic modifier of human bone cells. Mol Cell Endocrinol. 2013;369(1-2):27–34. doi:10.1016/j.mce.2013.02.002. These data demonstrate that epigenetic modulation of the sclerostin promoter contributes to the ability microenvironment factors to affect sclerostin expression.PubMedCrossRef

27.

Kamiya N, Ye L, Kobayashi T, Mochida Y, Yamauchi M, Kronenberg HM, et al. BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway. Development. 2008;135(22):3801–11. doi:10.1242/dev.025825.PubMedCentralPubMedCrossRef

28.

Papanicolaou SE, Phipps RJ, Fyhrie DP, Genetos DC. Modulation of sclerostin expression by mechanical loading and bone morphogenetic proteins in osteogenic cells. Biorheology. 2009;46(5):389–99. doi:10.3233/BIR-2009-0550.PubMed

29.••

Collette NM, Genetos DC, Economides AN, Xie L, Shahnazari M, Yao W, et al. Targeted deletion of SOST distal enhancer increases bone formation and bone mass. Proc Natl Acad Sci U S A. 2012;109(35):14092–7. doi:10.1073/pnas.1207188109. Deletion of the ECR5 enhancer region causes a bone phenotype similar to van Buchem's Disease.PubMedCentralPubMedCrossRef

30.

Leupin O, Kramer I, Collette NM, Loots GG, Natt F, Kneissel M, et al. Control of the SOST bone enhancer by PTH using MEF2 transcription factors. J Bone Min Res. 2007;22(12):1957–67. doi:10.1359/jbmr.070804.CrossRef

31.

Loots GG, Keller H, Leupin O, Murugesh D, Collette NM, Genetos DC. TGF-beta regulates sclerostin expression via the ECR5 enhancer. Bone. 2012;50(3):663–9. doi:10.1016/j.bone.2011.11.016.PubMedCentralPubMedCrossRef

32.

Quinn ZA, Yang CC, Wrana JL, McDermott JC. Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins. Nucleic Acids Res. 2001;29(3):732–42.PubMedCentralPubMedCrossRef

33.

Keller H, Kneissel M. SOST is a target gene for PTH in bone. Bone. 2005;37(2):148–58. doi:10.1016/j.bone.2005.03.018.PubMedCrossRef

34.

Genetos DC, Yellowley CE, Loots GG. Prostaglandin E2 signals through PTGER2 to regulate sclerostin expression. PLoS One. 2011;6(3):e17772. doi:10.1371/journal.pone.0017772.PubMedCentralPubMedCrossRef

35.

Ellies DL, Viviano B, McCarthy J, Rey JP, Itasaki N, Saunders S, et al. Bone density ligand, sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Min Res. 2006;21(11):1738–49. doi:10.1359/jbmr.060810.CrossRef

36.

Veverka V, Henry AJ, Slocombe PM, Ventom A, Mulloy B, Muskett FW, et al. 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):10890–900. doi:10.1074/jbc.M807994200.PubMedCrossRef

37.

Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. Embo J. 2003;22(23):6267–76. doi:10.1093/emboj/cdg599.PubMedCrossRef

38.

Collette NM, Genetos DC, Murugesh D, Harland RM, Loots GG. Genetic evidence that SOST inhibits WNT signaling in the limb. Dev Biol. 2010;342(2):169–79. doi:10.1016/j.ydbio.2010.03.021.PubMedCentralPubMedCrossRef

39.

Itasaki N, Jones CM, Mercurio S, Rowe A, Domingos PM, Smith JC, et al. Wise, a context-dependent activator and inhibitor of Wnt signalling. Development. 2003;130(18):4295–305.PubMedCrossRef

40.

Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005;280(20):19883–7. doi:10.1074/jbc.M413274200.PubMedCrossRef

41.•

Leupin O, Piters E, Halleux C, Hu S, Kramer I, Morvan F, et al. Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem. 2011;286(22):19489–500. doi:10.1074/jbc.M110.190330. This publication shows that interaction of sclerostin with LRP4 can also contribute to the regulation of human bone metabolism.PubMedCrossRef

42.•

Holdsworth G, Slocombe P, Doyle C, Sweeney B, Veverka V, Le Riche K, et al. Characterization of the interaction of sclerostin with the low density lipoprotein receptor-related protein (LRP) family of Wnt co-receptors. J Biol Chem. 2012;287(32):26464–77. doi:10.1074/jbc.M112.350108. These data characterize the binding of sclerostin to LRP.PubMedCrossRef

43.

Bourhis E, Wang W, Tam C, Hwang J, Zhang Y, Spittler D, et al. Wnt antagonists bind through a short peptide to the first beta-propeller domain of LRP5/6. Structure. 2011;19(10):1433–42. doi:10.1016/j.str.2011.07.005.PubMedCrossRef

44.

Semenov MV, He X. LRP5 mutations linked to high bone mass diseases cause reduced LRP5 binding and inhibition by SOST. J Biol Chem. 2006;281(50):38276–84. doi:10.1074/jbc.M609509200.PubMedCrossRef

45.

Sutherland MK, Geoghegan JC, Yu C, Turcott E, Skonier JE, Winkler DG, et al. Sclerostin promotes the apoptosis of human osteoblastic cells: a novel regulation of bone formation. Bone. 2004;35(4):828–35. doi:10.1016/j.bone.2004.05.023.PubMedCrossRef

46.

Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of SOST/sclerostin. J Biol Chem. 2008;283(9):5866–75. doi:10.1074/jbc.M705092200.PubMedCrossRef

47.••

Tu X, Rhee Y, Condon KW, Bivi N, Allen MR, Dwyer D, et al. SOST downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading. Bone. 2012;50(1):209–17. doi:10.1016/j.bone.2011.10.025. Transgenic SOST expression prevents the loading-induced osteogenic response, demonstrating that the modulation of SOST expression in osteocytes is a mechanism by which mechanical-loading stimulates bone formation.PubMedCentralPubMedCrossRef

48.

Lin C, Jiang X, Dai Z, Guo X, Weng T, Wang J, et al. Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Min Res. 2009;24(10):1651–61. doi:10.1359/jbmr.090411.CrossRef

49.

Galea GL, Sunters A, Meakin LB, Zaman G, Sugiyama T, Lanyon LE, et al. SOST down-regulation by mechanical strain in human osteoblastic cells involves PGE2 signaling via EP4. FEBS Lett. 2011;585(15):2450–4. doi:10.1016/j.febslet.2011.06.019.PubMedCentralPubMedCrossRef

50.

Nguyen J, Tang SY, Nguyen D, Alliston T. Load regulates bone formation and Sclerostin expression through a TGFbeta-dependent mechanism. PLoS One. 2013;8(1):e53813. doi:10.1371/journal.pone.0053813.PubMedCentralPubMedCrossRef

51.

Lips P, Courpron P, Meunier PJ. Mean wall thickness of trabecular bone packets in the human iliac crest: changes with age. Calcif Tissue Res. 1978;26(1):13–7.PubMedCrossRef

52.

Modder UI, Hoey KA, Amin S, McCready LK, Achenbach SJ, Riggs BL, et al. Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Min Res. 2011;26(2):373–9. doi:10.1002/jbmr.217.CrossRef

53.

Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ. Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS One. 2011;6(10):e25900. doi:10.1371/journal.pone.0025900.PubMedCentralPubMedCrossRef

54.

Kogawa M, Wijenayaka AR, Ormsby R, Thomas GP, Anderson PH, Bonewald LF, et al. Sclerostin regulates release of bone mineral by osteocytes by induction of carbonic anhydrase 2. J Bone Min Res. 2013;28:2436-2448 doi:10.1002/jbmr.2003.

55.

Qiang YW, Chen Y, Brown N, Hu B, Epstein J, Barlogie B, et al. Characterization of Wnt/beta-catenin signalling in osteoclasts in multiple myeloma. Br J Haematol. 2010;148(5):726–38. doi:10.1111/j.1365-2141.2009.08009.x.PubMedCentralPubMedCrossRef

56.

Ruan M, Pederson L, Hachfeld C, Thomson M, Prakash YS, Howe A, et al. Deletion of Wnt Receptors Lrp5 and Lrp6 or β-catenin in late osteoclast precursors differentially suppress osteoclast differentiation and bone metabolism. J Bone Miner Res. 2012;27(Suppl 1).

57.

Wei W, Zeve D, Suh JM, Wang X, Du Y, Zerwekh JE, et al. Biphasic and dosage-dependent regulation of osteoclastogenesis by beta-catenin. Mol Cell Biol. 2011;31(23):4706–19. doi:10.1128/MCB.05980-11.PubMedCentralPubMedCrossRef

58.

Otero K, Shinohara M, Zhao H, Cella M, Gilfillan S, Colucci A, et al. TREM2 and beta-catenin regulate bone homeostasis by controlling the rate of osteoclastogenesis. J Immunol. 2012;188(6):2612–21. doi:10.4049/jimmunol.1102836.PubMedCentralPubMedCrossRef

59.

Albers J, Keller J, Baranowsky A, Beil FT, Catala-Lehnen P, Schulze J, et al. Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin. J Cell Biol. 2013;200(4):537–49. doi:10.1083/jcb.201207142.PubMedCrossRef

60.

Kramer I, Loots GG, Studer A, Keller H, Kneissel M. Parathyroid hormone (PTH)–induced bone gain is blunted in SOST overexpressing and deficient mice. J Bone Min Res. 2010;25(2):178–89. doi:10.1359/jbmr.090730.CrossRef

61.

Cain CJ, Rueda R, McLelland B, Collette NM, Loots GG, Manilay JO. Absence of sclerostin adversely affects B-cell survival. J Bone Min Res. 2012;27(7):1451–61. doi:10.1002/jbmr.1608.CrossRef

62.

Brandenburg VM, Kramann R, Koos R, Kruger T, Schurgers L, Muhlenbruch G, et al. Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study. BMC Nephrol. 2013;14:219. doi:10.1186/1471-2369-14-219.PubMedCentralPubMedCrossRef

63.

Claes KJ, Viaene L, Heye S, Meijers B, d'Haese P, Evenepoel P. Sclerostin: another vascular calcification inhibitor? J Clin Endocrinol Metab. 2013;98(8):3221–8. doi:10.1210/jc.2013-1521.PubMedCrossRef

64.

Noordzij M, Cranenburg EM, Engelsman LF, Hermans MM, Boeschoten EW, Brandenburg VM, et al. Progression of aortic calcification is associated with disorders of mineral metabolism and mortality in chronic dialysis patients. Nephrol Dial Transplant. 2011;26(5):1662–9. doi:10.1093/ndt/gfq582.PubMedCrossRef

65.

Gardner J, van Bezooijen RL, Mervis B, Hamdy NAT, Lowik CWGM, Hamersma H, et al. Bone mineral density in sclerosteosis: affected individuals and gene carriers. J Clin Endo Metab. 2005;90(12):6392–5.CrossRef

66.

Li X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Min Res. 2009;24(4):578–88. doi:10.1359/jbmr.081206.CrossRef

67.

Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, et al. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Min Res. 2010;25(5):948–59. doi:10.1002/jbmr.14.CrossRef

68.

Tian X, Jee WS, Li X, Paszty C, Ke HZ. Sclerostin antibody increases bone mass by stimulating bone formation and inhibiting bone resorption in a hindlimb-immobilization rat model. Bone. 2011;48(2):197–201. doi:10.1016/j.bone.2010.09.009.PubMedCrossRef

69.••

Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Min Res. 2011;26(1):19–26. doi:10.1002/jbmr.173. The first-in-human study assessing the effects of sclerostin monoclonal antibody AMG 785 on the skeleton.CrossRef

70.••

McColm J, Hu L, Womack T, Tang CC, Chiang AY. Single- and multiple-dose randomized studies of blosozumab, a monoclonal antibody against sclerostin, in healthy postmenopausal women. J Bone Min Res. 2013. doi:10.1002/jbmr.2092. This study assesses the effects of the sclerostin monoclonal antibody blosozumab on the skeleton.

Titel: Developments in Sclerostin Biology: Regulation of Gene Expression, Mechanisms of Action, and Physiological Functions
verfasst von: Megan M. Weivoda
Merry Jo Oursler
Publikationsdatum: 01.03.2014
Verlag: Springer US
Erschienen in: Current Osteoporosis Reports / Ausgabe 1/2014
Print ISSN: 1544-1873
Elektronische ISSN: 1544-2241
DOI: https://doi.org/10.1007/s11914-014-0188-1

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