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| __NOTOC__
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| {{CMG}} {{AE}} {{JC}}
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| {{Pfam box |Symbol = Sclerostin |Name = Sclerostin |Pfam = PF05463 |InterPro = IPR008835 |PROSITE = |PDB = }}
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| ==Overview==
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| '''Sclerostin''' is a [[protein]] that in humans is encoded by the ''SOST'' [[gene]].<ref name="pmid11179006">{{cite journal | vauthors = Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo PJ, Fu Y, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan J | title = Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein | journal = American Journal of Human Genetics | volume = 68 | issue = 3 | pages = 577–89 | date = Mar 2001 | pmid = 11179006 | pmc = 1274471 | doi = 10.1086/318811 }}</ref><ref name="pmid11181578">{{cite journal | vauthors = 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, Foernzler D, Van Hul W | title = Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST) | journal = Human Molecular Genetics | volume = 10 | issue = 5 | pages = 537–43 | date = Mar 2001 | pmid = 11181578 | pmc = | doi = 10.1093/hmg/10.5.537 }}</ref>
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| Sclerostin is a secreted [[glycoprotein]] with a [[C-terminus|C-terminal]] [[cysteine knot]]-like (CTCK) domain and sequence similarity to the [[PARN|DAN]] (differential screening-selected gene aberrative in neuroblastoma) family of bone morphogenetic protein (BMP) antagonists. Sclerostin is produced by the [[osteocyte]] and has anti-anabolic effects on bone formation.<ref name="entrez">{{cite web | title = Entrez Gene: SOST sclerosteosis| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=50964| accessdate = }}</ref>
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| == Structure ==
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| The sclerostin protein, with a length of 213 residues, has a dssp secondary structure that is 28% [[beta sheet]] (6 strands; 32 residues).<ref name="pmid19166819"/>
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| == Function ==
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| Sclerostin, the product of the SOST gene, located on chromosome 17q12–q21 in humans,<ref name="Van Bezooijen2005">{{Cite journal | last1 = Van Bezooijen | first1 = R. L. | last2 = Papapoulos | first2 = S. E. | last3 = Hamdy | first3 = N. A. | last4 = Ten Dijke | first4 = P. | last5 = Löwik | first5 = C. W. | title = Control of bone formation by osteocytes? Lessons from the rare skeletal disorders sclerosteosis and van Buchem disease | doi = 10.1138/20050189 | journal = BoneKEy-Osteovision | volume = 2 | issue = 12 | pages = 33 | year = 2005 | pmid = | pmc = }}</ref> was originally believed to be a non-classical [[bone morphogenetic protein]] (BMP) antagonist.<ref name="pmid14633986">{{cite journal | vauthors = 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 | title = Osteocyte control of bone formation via sclerostin, a novel BMP antagonist | journal = The EMBO Journal | volume = 22 | issue = 23 | pages = 6267–76 | date = Dec 2003 | pmid = 14633986 | pmc = 291840 | doi = 10.1093/emboj/cdg599 }}</ref> More recently sclerostin has been identified as binding to [[LRP5]]/[[LRP6|6]] receptors and inhibiting the [[Wnt signaling pathway]].<ref name="pmid15778503"/><ref name="pmid17002572">{{cite journal | vauthors = Ellies DL, Viviano B, McCarthy J, Rey JP, Itasaki N, Saunders S, Krumlauf R | title = Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity | journal = Journal of Bone and Mineral Research | volume = 21 | issue = 11 | pages = 1738–49 | date = Nov 2006 | pmid = 17002572 | doi = 10.1359/jbmr.060810 }}</ref> The inhibition of the Wnt pathway leads to decreased bone formation.<ref name="pmid15778503">{{cite journal | vauthors = Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D | title = Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling | journal = The Journal of Biological Chemistry | volume = 280 | issue = 20 | pages = 19883–7 | date = May 2005 | pmid = 15778503 | doi = 10.1074/jbc.M413274200 }}</ref> Although the underlying mechanisms are unclear, it is believed that the antagonism of BMP-induced bone formation by sclerostin is mediated by Wnt signaling, but not BMP signaling pathways.<ref name="pmid17032150">{{cite journal | vauthors = van Bezooijen RL, Svensson JP, Eefting D, Visser A, van der Horst G, Karperien M, Quax PH, Vrieling H, Papapoulos SE, ten Dijke P, Löwik CW | title = Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation | journal = Journal of Bone and Mineral Research | volume = 22 | issue = 1 | pages = 19–28 | date = Jan 2007 | pmid = 17032150 | doi = 10.1359/jbmr.061002 }}</ref><ref name="pmid20952383">{{cite journal | vauthors = 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 | title = Distinct modes of inhibition by sclerostin on bone morphogenetic protein and Wnt signaling pathways | journal = The Journal of Biological Chemistry | volume = 285 | issue = 53 | pages = 41614–26 | date = Dec 2010 | pmid = 20952383 | pmc = 3009889 | doi = 10.1074/jbc.M110.153890 }}</ref> Sclerostin is expressed in [[osteocyte]]s and some [[chondrocyte]]s and it inhibits bone formation by [[osteoblast]]s.<ref name="pmid21254230">{{cite journal | vauthors = Bonewald LF | title = The amazing osteocyte | journal = Journal of Bone and Mineral Research | volume = 26 | issue = 2 | pages = 229–38 | date = Feb 2011 | pmid = 21254230 | pmc = 3179345 | doi = 10.1002/jbmr.320 }}</ref><ref name="pmid23470835">{{cite journal | vauthors = Burgers TA, Williams BO | title = Regulation of Wnt/β-catenin signaling within and from osteocytes | journal = Bone | volume = 54 | issue = 2 | pages = 244–9 | date = Jun 2013 | pmid = 23470835 | doi = 10.1016/j.bone.2013.02.022 }}</ref><ref name="pmid23017659">{{cite journal | vauthors = Bellido T, Saini V, Pajevic PD | title = Effects of PTH on osteocyte function | journal = Bone | volume = 54 | issue = 2 | pages = 250–7 | date = Jun 2013 | pmid = 23017659 | pmc = 3552098 | doi = 10.1016/j.bone.2012.09.016 }}</ref>
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| Sclerostin production by osteocytes is inhibited by [[parathyroid hormone]],<ref name="pmid23017659"/><ref name="pmid16081646">{{cite journal | vauthors = Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O'Brien CA, Manolagas SC, Jilka RL | title = Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis | journal = Endocrinology | volume = 146 | issue = 11 | pages = 4577–83 | date = Nov 2005 | pmid = 16081646 | doi = 10.1210/en.2005-0239 }}</ref> mechanical loading<ref name="pmid18089564">{{cite journal | vauthors = Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, Turner CH | title = Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin | journal = The Journal of Biological Chemistry | volume = 283 | issue = 9 | pages = 5866–75 | date = Feb 2008 | pmid = 18089564 | doi = 10.1074/jbc.M705092200 }}</ref> and cytokines including prostaglandin E2,<ref name="pmid21436889">{{cite journal | vauthors = Genetos DC, Yellowley CE, Loots GG | title = Prostaglandin E2 signals through PTGER2 to regulate sclerostin expression | journal = PLOS ONE | volume = 6 | issue = 3 | pages = e17772 | date = March 2011 | pmid = 21436889 | pmc = 3059227 | doi = 10.1371/journal.pone.0017772 }}</ref> [[oncostatin M]], [[cardiotrophin-1]] and [[leukemia inhibitory factor]].<ref name="pmid20051625">{{cite journal | vauthors = Walker EC, McGregor NE, Poulton IJ, Solano M, Pompolo S, Fernandes TJ, Constable MJ, Nicholson GC, Zhang JG, Nicola NA, Gillespie MT, Martin TJ, Sims NA | title = Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice | journal = The Journal of Clinical Investigation | volume = 120 | issue = 2 | pages = 582–92 | date = Feb 2010 | pmid = 20051625 | pmc = 2810087 | doi = 10.1172/JCI40568 }}</ref> Sclerostin production is increased by [[calcitonin]].<ref name="pmid20188226">{{cite journal | vauthors = Gooi JH, Pompolo S, Karsdal MA, Kulkarni NH, Kalajzic I, McAhren SH, Han B, Onyia JE, Ho PW, Gillespie MT, Walsh NC, Chia LY, Quinn JM, Martin TJ, Sims NA | title = Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes | journal = Bone | volume = 46 | issue = 6 | pages = 1486–97 | date = Jun 2010 | pmid = 20188226 | doi = 10.1016/j.bone.2010.02.018 }}</ref> Thus, osteoblast activity is self regulated by a negative feedback system.<ref>http://users.telenet.be/zeldzame.ziekten/List.o/Pmenoposteo.htm</ref>
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| == Clinical significance ==
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| Mutations in the gene sclerostin are associated with disorders associated with high bone mass, sclerosteosis and van Buchem disease.<ref name="Van Bezooijen2005"/> '''Sclerosteosis''' is an [[autosomal recessive]] disorder characterized by bone overgrowth. It was first described in 1958<ref name="Balemans2001">{{cite journal | vauthors = 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, Foernzler D, Van Hul W | title = Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST) | journal = Human Molecular Genetics | volume = 10 | issue = 5 | pages = 537–43 | date = Mar 2001 | pmid = 11181578 | doi = 10.1093/hmg/10.5.537 }}</ref><ref>{{cite journal | vauthors = Truswell AS | title = Osteopetrosis with syndactyly; a morphological variant of Albers-Schönberg's disease | journal = The Journal of Bone and Joint Surgery. British Volume | volume = 40-B | issue = 2 | pages = 209–18 | date = May 1958 | pmid = 13539104 }}</ref> but given the current name in 1967.<ref name="Balemans2002">{{cite journal | vauthors = Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C, Dioszegi M, Dikkers FG, Hildering P, Willems PJ, Verheij JB, Lindpaintner K, Vickery B, Foernzler D, Van Hul W | title = Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease | journal = Journal of Medical Genetics | volume = 39 | issue = 2 | pages = 91–7 | date = Feb 2002 | pmid = 11836356 | pmc = 1735035 | doi = 10.1136/jmg.39.2.91 }}</ref> Excessive bone formation is most prominent in the [[skull]], [[mandible]] and tubular bones.<ref name="Balemans2001"/> It can cause facial distortion and [[syndactyly]].<ref name="Balemans2001"/> Increased intracranial pressure can cause sudden death in patients.<ref name="Balemans2001"/> It is a rare disorder that is most prominent in the [[Afrikaner]] population in [[South Africa]] (40 patients), but there have also been cases of American and Brazilian families.<ref name="Balemans2001"/>
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| '''van Buchem disease''' is also an autosomal recessive skeletal disease characterized by bone overgrowth.<ref name="Balemans2002"/> It was first described in 1955 as "hyperostosis corticalis generalisata familiaris", but was given the current name in 1968.<ref name="Balemans2002"/><ref>{{cite journal | vauthors = Fosmoe RJ, Holm RS, Hildreth RC | title = Van Buchem's disease (hyperostosis corticalis generalisata familiaris). A case report | journal = Radiology | volume = 90 | issue = 4 | pages = 771–4 | date = Apr 1968 | pmid = 4867898 | doi = 10.1148/90.4.771 }}</ref> Excessive bone formation is most prominent in the skull, mandible, clavicle, ribs and [[diaphyses]] of long bones and bone formation occurs throughout life.<ref name="Balemans2002"/> It is a very rare condition with about 30 known cases in 2002.<ref name="Balemans2002"/> In 1967 van Buchem characterized the disease in 15 patients of Dutch origin.<ref name="Balemans2002"/> Patients with sclerosteosis are distinguished from those with van Buchem disease because they are often taller and have hand malformations.<ref name="Balemans2001"/>
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| An antibody for sclerostin is being developed because of the protein’s specificity to bone.<ref name="pmid21254230"/> Its use has increased bone growth in preclinical trials in osteoporotic rats and monkeys.<ref>{{cite journal | vauthors = 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 | title = Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis | journal = Journal of Bone and Mineral Research | volume = 24 | issue = 4 | pages = 578–88 | date = Apr 2009 | pmid = 19049336 | pmc = | doi = 10.1359/jbmr.081206 }}</ref><ref>{{cite journal | vauthors = 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 | title = Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength | journal = Journal of Bone and Mineral Research | volume = 25 | issue = 5 | pages = 948–59 | date = May 2010 | pmid = 20200929 | pmc = | doi = 10.1002/jbmr.14 }}</ref> In a [[Phases of clinical research#Phase I|Phase I study]], a single dose of anti-sclerostin [[antibody]] from [[Amgen]] ([[Romosozumab]]) increased bone density in the hip and spine in healthy men and postmenopausal women and the drug was well tolerated.<ref>{{cite journal | vauthors = Padhi D, Jang G, Stouch B, Fang L, Posvar E | title = Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody | journal = Journal of Bone and Mineral Research | volume = 26 | issue = 1 | pages = 19–26 | date = Jan 2011 | pmid = 20593411 | pmc = | doi = 10.1002/jbmr.173 }}</ref> In a Phase II trial, one year of the antibody treatment in osteoporotic women increased bone density more than [[bisphosphonate]] and [[teriparatide]] treatment; it had mild injection side effects.<ref name="pmid23470835"/><ref>{{cite journal | last1 = Reid | first1 = I. R. | title = Osteoporosis treatment at ASBMR 2012 | journal = IBMS BoneKEy | volume = 9 | year = 2012 | pmid = | pmc = | doi = 10.1038/bonekey.2012.245 }}</ref> A Phase II trial of a monoclonal human antibody to sclerostin from [[Eli Lilly and Company|Eli Lilly]] had positive effects on post-menopausal women. Monthly treatments of the antibody for one year increased the bone mineral density of the spine and hip by 18 percent and 6 percent, respectively, compared to the placebo group.<ref>{{cite journal | vauthors = Recker RR, Benson CT, Matsumoto T, Bolognese MA, Robins DA, Alam J, Chiang AY, Hu L, Krege JH, Sowa H, Mitlak BH, Myers SL | title = A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density | journal = Journal of Bone and Mineral Research | volume = 30 | issue = 2 | pages = 216–24 | date = Feb 2015 | pmid = 25196993 | doi = 10.1002/jbmr.2351 }}</ref>
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| The Amgen drug is expected to be on the market in 2017 and is predicted to be the gold standard in osteoporosis treatment by 2021.<ref>{{cite web |url= http://www.marketwatch.com/story/for-osteoporosis-and-osteopenia-clinical-data-and-thought-leaders-opinions-indicate-that-amg-785cdp-7851-and-odanacatib-have-advantages-over-alendronate-2013-04-04 |title= For Osteoporosis and Osteopenia, Clinical Data and Thought Leaders' Opinions Indicate that AMG-785/CDP-7851 and Odanacatib Have Advantages Over Alendronate |date= 2013-04-04 |accessdate= 2013-04-20 |publisher= PR Newswire}}</ref> In addition, OsteoGeneX is developing small molecule inhibitors of sclerostin.<ref name="pmid20014100">{{cite journal | vauthors = Rey JP, Ellies DL | title = Wnt modulators in the biotech pipeline | journal = Developmental Dynamics | volume = 239 | issue = 1 | pages = 102–14 | date = Jan 2010 | pmid = 20014100 | pmc = 3111251 | doi = 10.1002/dvdy.22181 }}</ref>
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| == References ==
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| {{reflist|33em}}
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| == Further reading ==
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| {{refbegin|33em}}
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| * {{cite journal | vauthors = Balemans W, Van Hul W | title = Human genetics of SOST | journal = Journal of Musculoskeletal & Neuronal Interactions | volume = 6 | issue = 4 | pages = 355–6 | year = 2007 | pmid = 17185822 | doi = }}
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| * {{cite journal | vauthors = Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C, Dioszegi M, Dikkers FG, Hildering P, Willems PJ, Verheij JB, Lindpaintner K, Vickery B, Foernzler D, Van Hul W | title = Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease | journal = Journal of Medical Genetics | volume = 39 | issue = 2 | pages = 91–7 | date = Feb 2002 | pmid = 11836356 | pmc = 1735035 | doi = 10.1136/jmg.39.2.91 }}
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| * {{cite journal | vauthors = Staehling-Hampton K, Proll S, Paeper BW, Zhao L, Charmley P, Brown A, Gardner JC, Galas D, Schatzman RC, Beighton P, Papapoulos S, Hamersma H, Brunkow ME | title = A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population | journal = American Journal of Medical Genetics | volume = 110 | issue = 2 | pages = 144–52 | date = Jun 2002 | pmid = 12116252 | doi = 10.1002/ajmg.10401 }}
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| * {{cite journal | vauthors = Balemans W, Foernzler D, Parsons C, Ebeling M, Thompson A, Reid DM, Lindpaintner K, Ralston SH, Van Hul W | title = Lack of association between the SOST gene and bone mineral density in perimenopausal women: analysis of five polymorphisms | journal = Bone | volume = 31 | issue = 4 | pages = 515–9 | date = Oct 2002 | pmid = 12398949 | doi = 10.1016/S8756-3282(02)00844-X }}
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| * {{cite journal | vauthors = Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A | title = The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment | journal = Genome Research | volume = 13 | issue = 10 | pages = 2265–70 | date = Oct 2003 | pmid = 12975309 | pmc = 403697 | doi = 10.1101/gr.1293003 }}
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| * {{cite journal | vauthors = Sevetson B, Taylor S, Pan Y | title = Cbfa1/RUNX2 directs specific expression of the sclerosteosis gene (SOST) | journal = The Journal of Biological Chemistry | volume = 279 | issue = 14 | pages = 13849–58 | date = Apr 2004 | pmid = 14739291 | doi = 10.1074/jbc.M306249200 }}
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| * {{cite journal | vauthors = van Bezooijen RL, Roelen BA, Visser A, van der Wee-Pals L, de Wilt E, Karperien M, Hamersma H, Papapoulos SE, ten Dijke P, Löwik CW | title = Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist | journal = The Journal of Experimental Medicine | volume = 199 | issue = 6 | pages = 805–14 | date = Mar 2004 | pmid = 15024046 | pmc = 2212719 | doi = 10.1084/jem.20031454 }}
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| * {{cite journal | vauthors = Winkler DG, Yu C, Geoghegan JC, Ojala EW, Skonier JE, Shpektor D, Sutherland MK, Latham JA | title = Noggin and sclerostin bone morphogenetic protein antagonists form a mutually inhibitory complex | journal = The Journal of Biological Chemistry | volume = 279 | issue = 35 | pages = 36293–8 | date = Aug 2004 | pmid = 15199066 | doi = 10.1074/jbc.M400521200 }}
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| * {{cite journal | vauthors = Zhang Z, Henzel WJ | title = Signal peptide prediction based on analysis of experimentally verified cleavage sites | journal = Protein Science | volume = 13 | issue = 10 | pages = 2819–24 | date = Oct 2004 | pmid = 15340161 | pmc = 2286551 | doi = 10.1110/ps.04682504 }}
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| * {{cite journal | vauthors = Sutherland MK, Geoghegan JC, Yu C, Turcott E, Skonier JE, Winkler DG, Latham JA | title = Sclerostin promotes the apoptosis of human osteoblastic cells: a novel regulation of bone formation | journal = Bone | volume = 35 | issue = 4 | pages = 828–35 | date = Oct 2004 | pmid = 15454089 | doi = 10.1016/j.bone.2004.05.023 }}
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| * {{cite journal | vauthors = 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 | title = Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites | journal = American Journal of Human Genetics | volume = 75 | issue = 6 | pages = 1032–45 | date = Dec 2004 | pmid = 15514891 | pmc = 1182139 | doi = 10.1086/426458 }}
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| * {{cite journal | vauthors = Winkler DG, Sutherland MS, Ojala E, Turcott E, Geoghegan JC, Shpektor D, Skonier JE, Yu C, Latham JA | title = Sclerostin inhibition of Wnt-3a-induced C3H10T1/2 cell differentiation is indirect and mediated by bone morphogenetic proteins | journal = The Journal of Biological Chemistry | volume = 280 | issue = 4 | pages = 2498–502 | date = Jan 2005 | pmid = 15545262 | doi = 10.1074/jbc.M400524200 }}
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| * {{cite journal | vauthors = Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Löwik CW, Reeve J | title = Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation | journal = FASEB Journal | volume = 19 | issue = 13 | pages = 1842–4 | date = Nov 2005 | pmid = 16123173 | doi = 10.1096/fj.05-4221fje }}
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| * {{cite journal | vauthors = Gardner JC, van Bezooijen RL, Mervis B, Hamdy NA, Löwik CW, Hamersma H, Beighton P, Papapoulos SE | title = Bone mineral density in sclerosteosis; affected individuals and gene carriers | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 90 | issue = 12 | pages = 6392–5 | date = Dec 2005 | pmid = 16189254 | doi = 10.1210/jc.2005-1235 }}
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| {{refend}}
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| == External links ==
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| *[http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=sost GeneReview/NCBI/NIH/UW entry on SOST-Related Sclerosing Bone Dysplasias]
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| [[Category:Human proteins]]
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| [[Category:Osteopathies]]
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