Sost

Summary

Gene Symbol: Sost
Description: sclerostin
Alias: 5430411E23Rik, sclerostin
Species: mouse
Products:     Sost

Top Publications

  1. Robling A, Bellido T, Turner C. Mechanical stimulation in vivo reduces osteocyte expression of sclerostin. J Musculoskelet Neuronal Interact. 2006;6:354 pubmed
  2. Bellido T. Downregulation of SOST/sclerostin by PTH: a novel mechanism of hormonal control of bone formation mediated by osteocytes. J Musculoskelet Neuronal Interact. 2006;6:358-9 pubmed
  3. Leupin O, Kramer I, Collette N, Loots G, Natt F, Kneissel M, et al. Control of the SOST bone enhancer by PTH using MEF2 transcription factors. J Bone Miner Res. 2007;22:1957-67 pubmed
    Expression of the osteocyte-derived bone formation inhibitor sclerostin in adult bone requires a distant enhancer. We show that MEF2 transcription factors control this enhancer and mediate inhibition of sclerostin expression by PTH...
  4. Robling A, Niziolek P, Baldridge L, Condon K, Allen M, Alam I, et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem. 2008;283:5866-75 pubmed
    b>Sclerostin, the protein product of the Sost gene, is a potent inhibitor of bone formation...
  5. Li X, Ominsky M, Niu Q, Sun N, Daugherty B, D Agostin D, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res. 2008;23:860-9 pubmed publisher
    ..is a rare high bone mass genetic disorder in humans caused by inactivating mutations in SOST, the gene encoding sclerostin. Based on these data, sclerostin has emerged as a key negative regulator of bone mass...
  6. 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;278:24113-7 pubmed
    Sclerosteosis is a progressive sclerosing bone dysplasia. Sclerostin (the SOST gene) was originally identified as the sclerosteosis-causing gene. However, the physiological role of sclerostin remains to be elucidated...
  7. Winkler D, Sutherland M, Geoghegan J, Yu C, Hayes T, Skonier J, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003;22:6267-76 pubmed
    ..Sclerosteosis is a disease typified by high bone mass due to the loss of SOST expression. Sclerostin, the SOST gene protein product, competed with the type I and type II bone morphogenetic protein (BMP) receptors ..
  8. 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 Miner Res. 2009;24:1651-61 pubmed publisher
    ..We showed that sclerostin selectively inhibited Wnt/beta-catenin in vivo, and sclerostin suppressed the activity of osteoblast and ..
  9. Choi H, 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:e7930 pubmed publisher
    ..b>Sclerostin is a potent osteocyte secreted inhibitor of bone formation that directly binds Lrp5 and Lrp6 and modulates both ..

More Information

Publications87

  1. Brunkow M, Gardner J, Van Ness J, Paeper B, Kovacevich B, 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 pubmed
    ..Here we report two independent mutations in a novel gene, termed "SOST." Affected Afrikaners carry a nonsense mutation near the amino terminus of the encoded protein, whereas an ..
  2. Van Dinther M, Zhang J, Weidauer S, Boschert V, Muth E, Knappik A, et al. Anti-Sclerostin antibody inhibits internalization of Sclerostin and Sclerostin-mediated antagonism of Wnt/LRP6 signaling. PLoS ONE. 2013;8:e62295 pubmed publisher
    ..Its gene product, Sclerostin, is a key negative regulator of bone formation and might therefore serve as a target for the anabolic treatment ..
  3. Kramer I, Loots G, Studer A, Keller H, Kneissel M. Parathyroid hormone (PTH)-induced bone gain is blunted in SOST overexpressing and deficient mice. J Bone Miner Res. 2010;25:178-89 pubmed publisher
    ..PTH) treatment is a potent bone anabolic principle that suppresses expression of the bone formation inhibitor Sost. We addressed the relevance of Sost suppression for PTH-induced bone anabolism in vivo using mice with altered Sost ..
  4. Balemans W, Piters E, Cleiren E, Ai M, Van Wesenbeeck L, Warman M, et al. The binding between sclerostin and LRP5 is altered by DKK1 and by high-bone mass LRP5 mutations. Calcif Tissue Int. 2008;82:445-53 pubmed publisher
    ..present study, we investigated six different HBM-LRP5 mutations and confirm that neither Dickkopf1 (DKK1) nor sclerostin efficiently inhibits HBM-LRP5 signaling...
  5. Tu X, Rhee Y, Condon K, Bivi N, Allen M, Dwyer D, et al. Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading. Bone. 2012;50:209-17 pubmed publisher
    b>Sclerostin, the Wnt signaling antagonist encoded by the Sost gene, is secreted by osteocytes and inhibits bone formation by osteoblasts...
  6. 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;145:4685-92 pubmed
    b>Sclerostin (SOST), a member of the cystine-knot superfamily, is essential for proper skeletogenesis because a loss-of-function mutation in the SOST gene results in sclerosteosis featured with massive bone growth in humans...
  7. van Bezooijen R, Svensson J, Eefting D, Visser A, van der Horst G, Karperien M, et al. Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation. J Bone Miner Res. 2007;22:19-28 pubmed
    b>Sclerostin is an osteocyte-derived negative regulator of bone formation. It inhibits BMP-stimulated bone formation both in vitro and in vivo but has no direct effect on BMP signaling...
  8. Krause C, Korchynskyi O, de Rooij K, Weidauer S, de Gorter D, van Bezooijen R, et al. Distinct modes of inhibition by sclerostin on bone morphogenetic protein and Wnt signaling pathways. J Biol Chem. 2010;285:41614-26 pubmed publisher
    b>Sclerostin is expressed by osteocytes and has catabolic effects on bone. It has been shown to antagonize bone morphogenetic protein (BMP) and/or Wnt activity, although at present the underlying mechanisms are unclear...
  9. Weidauer S, Schmieder P, Beerbaum M, Schmitz W, Oschkinat H, Mueller T. NMR structure of the Wnt modulator protein Sclerostin. Biochem Biophys Res Commun. 2009;380:160-5 pubmed publisher
    b>Sclerostin has been identified as a negative regulator of bone growth...
  10. Ellies D, Viviano B, McCarthy J, Rey J, Itasaki N, Saunders S, et al. Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res. 2006;21:1738-49 pubmed
    We compared and contrasted the mechanism of action for the cysteine knot protein subfamily, Wise and Sost (Sclerostin)...
  11. Loots G, Kneissel M, Keller H, Baptist M, Chang J, Collette N, et al. Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. Genome Res. 2005;15:928-35 pubmed
    ..Using BAC recombination and transgenesis, we characterized the expression of human sclerostin (SOST) from normal (SOST(wt)) or Van Buchem (SOST(vbDelta) alleles...
  12. Keller H, Kneissel M. SOST is a target gene for PTH in bone. Bone. 2005;37:148-58 pubmed
    ..Yet, the molecular mechanisms underlying this bone anabolic action are not fully understood. Recently, SOST (sclerostin) was identified as a potent osteocyte expressed negative regulator of bone formation in vitro, in murine models ..
  13. Winkler D, Sutherland M, Ojala E, Turcott E, Geoghegan J, Shpektor D, et al. Sclerostin inhibition of Wnt-3a-induced C3H10T1/2 cell differentiation is indirect and mediated by bone morphogenetic proteins. J Biol Chem. 2005;280:2498-502 pubmed
    ..Surprisingly, sclerostin, noggin, and human BMP receptor 1A (BMPR1A)-FC fusion proteins blocked Wnt-3A-induced ALP as well as BMP-6-..
  14. Bellido T, Ali A, Gubrij I, Plotkin L, Fu Q, O Brien C, et al. Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology. 2005;146:4577-83 pubmed
    ..This effect was accompanied by a comparable reduction of sclerostin, the product of Sost, in osteocytes, as determined by quantitative immunoblot analysis of bone extracts and by ..
  15. Li C, Ominsky M, Tan H, Barrero M, Niu Q, Asuncion F, et al. Increased callus mass and enhanced strength during fracture healing in mice lacking the sclerostin gene. Bone. 2011;49:1178-85 pubmed publisher
    Humans with inherited sclerostin deficiency have high bone mass. Targeted deletion of the sclerostin gene in mice (SOST-KO) causes increases in bone formation, bone mass and bone strength...
  16. Yorgan T, Peters S, Jeschke A, Benisch P, Jakob F, Amling M, et al. The Anti-Osteoanabolic Function of Sclerostin Is Blunted in Mice Carrying a High Bone Mass Mutation of Lrp5. J Bone Miner Res. 2015;30:1175-83 pubmed publisher
    Activating mutations of the putative Wnt co-receptor Lrp5 or inactivating mutations of the secreted molecule Sclerostin cause excessive bone formation in mice and humans...
  17. Collette N, Genetos D, Economides A, 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;109:14092-7 pubmed publisher
    ..In humans, lack of Sclerostin causes sclerosteosis and van Buchem (VB) disease, two generalized skeletal hyperostosis disorders that result ..
  18. Roudier M, Li X, Niu Q, Pacheco E, Pretorius J, Graham K, et al. Sclerostin is expressed in articular cartilage but loss or inhibition does not affect cartilage remodeling during aging or following mechanical injury. Arthritis Rheum. 2013;65:721-31 pubmed publisher
    b>Sclerostin plays a major role in regulating skeletal bone mass, but its effects in articular cartilage are not known...
  19. Kamiya N, Kobayashi T, Mochida Y, Yu P, Yamauchi M, Kronenberg H, et al. Wnt inhibitors Dkk1 and Sost are downstream targets of BMP signaling through the type IA receptor (BMPRIA) in osteoblasts. J Bone Miner Res. 2010;25:200-10 pubmed publisher
    ..type IA (BMPRIA) resulted in increased bone mass during embryonic development, where diminished expression of Sost as a downstream effector of BMPRIA resulted in increased Wnt/beta-catenin signaling...
  20. Chang M, Kramer I, Keller H, Gooi J, Collett C, Jenkins D, et al. Reversing LRP5-dependent osteoporosis and SOST deficiency-induced sclerosing bone disorders by altering WNT signaling activity. J Bone Miner Res. 2014;29:29-42 pubmed publisher
    The bone formation inhibitor sclerostin encoded by SOST binds in vitro to low-density lipoprotein receptor-related protein (LRP) 5/6 Wnt co-receptors, thereby inhibiting Wnt/?-catenin signaling, a central pathway of skeletal homeostasis...
  21. Saidak Z, Le Henaff C, Azzi S, Marty C, Marie P. Low-dose PTH increases osteoblast activity via decreased Mef2c/Sost in senescent osteopenic mice. J Endocrinol. 2014;223:25-33 pubmed publisher
    ..Moreover, low-dose PTH decreased the expression of the Mef2c transcription factor, resulting in decreased Sost expression in osteoblasts/osteocytes...
  22. Baek K, Hwang H, Park H, Kwon A, Qadir A, Ko S, et al. TNF-? upregulates sclerostin expression in obese mice fed a high-fat diet. J Cell Physiol. 2014;229:640-50 pubmed publisher
    b>Sclerostin decreases bone mass by antagonizing the Wnt signaling pathway. We examined whether obesity-induced bone loss is associated with the expression of sclerostin...
  23. Chen J, Kamiya Y, Polur I, Xu M, Choi T, Kalajzic Z, et al. Estrogen via estrogen receptor beta partially inhibits mandibular condylar cartilage growth. Osteoarthritis Cartilage. 2014;22:1861-8 pubmed publisher
    ..in ovariectomized WT mice caused a significant decrease in ER alpha expression and a significant increase in Sost expression compared with ovariectomized mice treated with placebo...
  24. Ellies D, Economou A, Viviano B, Rey J, Paine Saunders S, Krumlauf R, et al. Wise regulates bone deposition through genetic interactions with Lrp5. PLoS ONE. 2014;9:e96257 pubmed publisher
    ..Wise and the closely related protein Sclerostin (Sost) are expressed in osteoblast cells during temporally distinct early and late phases in a manner consistent ..
  25. Kamiya N, Shuxian L, Yamaguchi R, Phipps M, Aruwajoye O, Adapala N, et al. Targeted disruption of BMP signaling through type IA receptor (BMPR1A) in osteocyte suppresses SOST and RANKL, leading to dramatic increase in bone mass, bone mineral density and mechanical strength. Bone. 2016;91:53-63 pubmed publisher
    ..Molecular studies demonstrated a significant decrease in the Sost mRNA levels in bone (>95%), and the SOST protein levels in serum (~85%) and bone matrices...
  26. Spatz J, Wein M, Gooi J, Qu Y, Garr J, Liu S, et al. The Wnt Inhibitor Sclerostin Is Up-regulated by Mechanical Unloading in Osteocytes in Vitro. J Biol Chem. 2015;290:16744-58 pubmed publisher
    ..b>Sclerostin, a product of the SOST gene, is produced postnatally primarily by osteocytes and is a negative regulator of bone ..
  27. Ota K, Quint P, Ruan M, Pederson L, Westendorf J, Khosla S, et al. Sclerostin is expressed in osteoclasts from aged mice and reduces osteoclast-mediated stimulation of mineralization. J Cell Biochem. 2013;114:1901-1907 pubmed publisher
    ..Gene and protein analysis revealed that the Wnt antagonist sclerostin was significantly elevated in the conditioned media from 24-month-old mouse cells compared to 6-week-old mouse ..
  28. Hassler N, Roschger A, Gamsjaeger S, Kramer I, Lueger S, van Lierop A, et al. Sclerostin deficiency is linked to altered bone composition. J Bone Miner Res. 2014;29:2144-51 pubmed publisher
    High bone mass in animals and humans with sclerostin deficiency is associated with increased bone strength, which is not the case for all disorders with high bone mineral density, some of which are even associated with fragility fractures ..
  29. Bonnet N, Standley K, Bianchi E, Stadelmann V, Foti M, Conway S, et al. The matricellular protein periostin is required for sost inhibition and the anabolic response to mechanical loading and physical activity. J Biol Chem. 2009;284:35939-50 pubmed publisher
    ..Furthermore, we administered a sclerostin-blocking antibody to these mice in order to demonstrate the influence of sustained Sost expression in their ..
  30. Moriishi T, Fukuyama R, Ito M, Miyazaki T, Maeno T, Kawai Y, et al. Osteocyte network; a negative regulatory system for bone mass augmented by the induction of Rankl in osteoblasts and Sost in osteocytes at unloading. PLoS ONE. 2012;7:e40143 pubmed publisher
    ..b>Sost was locally induced at unloading in wild-type mice but not in BCL2 transgenic mice, and the dissemination of Sost ..
  31. Jastrzebski S, Kalinowski J, Stolina M, Mirza F, Torreggiani E, Kalajzic I, et al. Changes in bone sclerostin levels in mice after ovariectomy vary independently of changes in serum sclerostin levels. J Bone Miner Res. 2013;28:618-26 pubmed publisher
    We examined the effects that ovariectomy had on sclerostin mRNA and protein levels in the bones of 8-week-old mice that were either sham-operated (SHAM) or ovariectomized (OVX) and then euthanized 3 or 6 weeks later...
  32. Marenzana M, Vugler A, Moore A, Robinson M. Effect of sclerostin-neutralising antibody on periarticular and systemic bone in a murine model of rheumatoid arthritis: a microCT study. Arthritis Res Ther. 2013;15:R125 pubmed
    ..We have previously shown that treatment with sclerostin antibody (Scl-AbI) builds bone and can prevent or restore bone loss in a murine model of inflammatory bowel ..
  33. Morse A, Yu N, Peacock L, Mikulec K, Kramer I, Kneissel M, et al. Endochondral fracture healing with external fixation in the Sost knockout mouse results in earlier fibrocartilage callus removal and increased bone volume fraction and strength. Bone. 2015;71:155-63 pubmed publisher
    b>Sclerostin deficiency, via genetic knockout or anti-Sclerostin antibody treatment, has been shown to cause increased bone volume, density and strength of calluses following endochondral bone healing...
  34. Sato A, Cregor M, Delgado Calle J, Condon K, Allen M, Peacock M, et al. Protection From Glucocorticoid-Induced Osteoporosis by Anti-Catabolic Signaling in the Absence of Sost/Sclerostin. J Bone Miner Res. 2016;31:1791-1802 pubmed publisher
    ..In WT mice, glucocorticoids increased the expression of Sost and the number of sclerostin-positive osteocytes, and altered the molecular signature of the Wnt/β-catenin pathway by decreasing the ..
  35. Jheon A, Mostowfi P, Snead M, Ihrie R, Sone E, Pramparo T, et al. PERP regulates enamel formation via effects on cell-cell adhesion and gene expression. J Cell Sci. 2011;124:745-54 pubmed publisher
    ..Together, our data show that PERP is necessary for the integrity of the ameloblast-SI interface and that a lack of Perp causes downregulation of genes that are required for proper enamel formation. ..
  36. Dai X, Jiang W, Zhang Q, Xu L, Geng P, Zhuang S, et al. Requirement for integrin-linked kinase in neural crest migration and differentiation and outflow tract morphogenesis. BMC Biol. 2013;11:107 pubmed publisher
    ..Changes in these pathways may collectively result in the unique neural crest and outflow tract phenotypes observed in ILK mutants. ..
  37. Robling A, Kang K, Bullock W, Foster W, Murugesh D, Loots G, et al. Sost, independent of the non-coding enhancer ECR5, is required for bone mechanoadaptation. Bone. 2016;92:180-188 pubmed publisher
    b>Sclerostin (Sost) is a negative regulator of bone formation that acts upon the Wnt signaling pathway...
  38. Galea G, Meakin L, Sugiyama T, Zebda N, Sunters A, Taipaleenmaki H, et al. Estrogen receptor ? mediates proliferation of osteoblastic cells stimulated by estrogen and mechanical strain, but their acute down-regulation of the Wnt antagonist Sost is mediated by estrogen receptor ?. J Biol Chem. 2013;288:9035-48 pubmed publisher
    ..proliferation through estrogen receptor (ER)-mediated effects, and both down-regulate the Wnt antagonist Sost/sclerostin. Here, we investigate the differential effects of ER? and -? in these processes in mouse long bone-derived ..
  39. Chang M, Kramer I, Huber T, Kinzel B, Guth Gundel S, Leupin O, et al. Disruption of Lrp4 function by genetic deletion or pharmacological blockade increases bone mass and serum sclerostin levels. Proc Natl Acad Sci U S A. 2014;111:E5187-95 pubmed publisher
    ..LRP4 (low-density lipoprotein receptor-related protein 4) as a facilitator of the WNT (Wingless-type) antagonist sclerostin and found mutations disrupting this function to be associated with high bone mass in humans similar to patients ..
  40. Pederson L, Ruan M, Westendorf J, Khosla S, Oursler M. Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. Proc Natl Acad Sci U S A. 2008;105:20764-9 pubmed publisher
    ..Wnt10b and BMP6 also were significantly increased in mature osteoclasts, whereas sclerostin levels decreased during differentiation...
  41. Haynes K, Pettit A, Duan R, Tseng H, Glant T, Brown M, et al. Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors. Arthritis Res Ther. 2012;14:R253 pubmed publisher
    ..Expression levels of DKK1 and SOST, Wnt signalling inhibitors highly expressed in joints, were reduced by 49% and 63% respectively in the spine PGISp ..
  42. Zanotti S, Canalis E. The Dmp1-SOST Transgene Interacts With and Downregulates the Dmp1-Cre Transgene and the Rosa(Notch) Allele. J Cell Biochem. 2016;117:1222-32 pubmed publisher
    ..targeted to the reverse orientation splice acceptor (Rosa)26 locus, causes osteopetrosis associated with suppressed Sost expression and enhanced Wnt signaling...
  43. Yoon J, Feng X, Kim Y, Shin D, Hatzi K, Wang H, et al. Interferon regulatory factor 8 (IRF8) interacts with the B cell lymphoma 6 (BCL6) corepressor BCOR. J Biol Chem. 2014;289:34250-7 pubmed publisher
    ..Taken together, these data suggest that a complex comprising BCOR-BCL6-IRF8 modulates BCL6-associated transcriptional regulation of germinal center B cell function. ..
  44. Wang L, Wu H, Xu Y, Deng M, Han X, Bai D. Effect of SOST gene deletion on the progression of renal interstitial fibrosis in obstructive kidney injury. Ren Fail. 2015;37:1514-7 pubmed publisher
    The role of SOST/sclerostin in mediating tissue fibrogenic response to injury/inflammation remains largely unknown...
  45. Collignon A, Amri N, Lesieur J, Sadoine J, Ribes S, Menashi S, et al. Sclerostin Deficiency Promotes Reparative Dentinogenesis. J Dent Res. 2017;96:815-821 pubmed publisher
    In humans, the SOST gene encodes sclerostin, an inhibitor of bone growth and remodeling, which also negatively regulates the bone repair process...
  46. Amri N, Djolé S, Petit S, Babajko S, Coudert A, Castaneda B, et al. Distorted Patterns of Dentinogenesis and Eruption in Msx2 Null Mutants: Involvement of Sost/Sclerostin. Am J Pathol. 2016;186:2577-87 pubmed publisher
    ..Of three inhibitors of Wnt/?-catenin signaling (Dkk1, SostDc1, and Sost/Sclerostin), only Sost was expressed in postnatal teeth and overexpressed in Msx2(-/-) tooth samples...
  47. Ren Y, Han X, Ho S, Harris S, Cao Z, Economides A, et al. Removal of SOST or blocking its product sclerostin rescues defects in the periodontitis mouse model. FASEB J. 2015;29:2702-11 pubmed publisher
    ..Importantly, we proved that deleting the Sost gene (a potent inhibitor of WNT signaling) or blocking sclerostin function by using the mAb in this periodontitis model significantly restores bone and PDL defects (n = 4-5; P &..
  48. Jáuregui E, Akil O, Acevedo C, Hall Glenn F, Tsai B, Bale H, et al. Parallel mechanisms suppress cochlear bone remodeling to protect hearing. Bone. 2016;89:7-15 pubmed publisher
    ..Understanding the cellular and molecular mechanisms that confer site-specific control of bone remodeling has the potential to elucidate new pathways that are deregulated in skeletal disease. ..
  49. Yokomoto Umakoshi M, Kanazawa I, Takeno A, Tanaka K, Notsu M, Sugimoto T. Activation of AMP-activated protein kinase decreases receptor activator of NF-κB ligand expression and increases sclerostin expression by inhibiting the mevalonate pathway in osteocytic MLO-Y4 cells. Biochem Biophys Res Commun. 2016;469:791-6 pubmed publisher
    ..the effects of AMPK activation on the expression of receptor activator of NF-κB ligand (RANKL) and sclerostin in osteocytes...
  50. Holmes G, Rothschild G, Roy U, Deng C, Mansukhani A, Basilico C. Early onset of craniosynostosis in an Apert mouse model reveals critical features of this pathology. Dev Biol. 2009;328:273-84 pubmed publisher
  51. Collette N, Yee C, Murugesh D, Sebastian A, Taher L, Gale N, et al. Sost and its paralog Sostdc1 coordinate digit number in a Gli3-dependent manner. Dev Biol. 2013;383:90-105 pubmed publisher
    ..Here we show that Sost and its paralog Sostdc1 emerged through ancestral genome duplication and their expression patterns have diverged to ..
  52. Artsi H, Cohen Kfir E, Gurt I, Shahar R, Bajayo A, Kalish N, et al. The Sirtuin1 activator SRT3025 down-regulates sclerostin and rescues ovariectomy-induced bone loss and biomechanical deterioration in female mice. Endocrinology. 2014;155:3508-15 pubmed publisher
    Estrogen deficiency leads to rapid bone loss and skeletal fragility. Sclerostin, encoded by the sost gene, and a product of the osteocyte, is a negative regulator of bone formation...
  53. Ukita M, Yamaguchi T, Ohata N, Tamura M. Sclerostin Enhances Adipocyte Differentiation in 3T3-L1 Cells. J Cell Biochem. 2016;117:1419-28 pubmed publisher
    b>Sclerostin, a secreted protein encoded by the Sost gene, is produced by osteocytes and is inhibited by osteoblast differentiation and bone formation...
  54. Alzahrani M, Rauch F, Hamdy R. Does Sclerostin Depletion Stimulate Fracture Healing in a Mouse Model?. Clin Orthop Relat Res. 2016;474:1294-302 pubmed publisher
    b>Sclerostin is a secreted glycoprotein that inhibits the intracellular Wnt signaling pathway, which, when inactivated, stimulates bone formation...
  55. Kedlaya R, Veera S, Horan D, Moss R, Ayturk U, Jacobsen C, et al. Sclerostin inhibition reverses skeletal fragility in an Lrp5-deficient mouse model of OPPG syndrome. Sci Transl Med. 2013;5:211ra158 pubmed publisher
    ..WNT signaling through LRP5, and also through the closely related receptor LRP6, is inhibited by the protein sclerostin (SOST)...
  56. Kim S, Frey J, Li Z, Kushwaha P, Zoch M, Tomlinson R, et al. Sclerostin influences body composition by regulating catabolic and anabolic metabolism in adipocytes. Proc Natl Acad Sci U S A. 2017;114:E11238-E11247 pubmed publisher
    b>Sclerostin has traditionally been thought of as a local inhibitor of bone acquisition that antagonizes the profound osteoanabolic capacity of activated Wnt/?-catenin signaling, but serum sclerostin levels in humans exhibit a correlation ..
  57. Niziolek P, MacDonald B, Kedlaya R, Zhang M, Bellido T, He X, et al. High Bone Mass-Causing Mutant LRP5 Receptors Are Resistant to Endogenous Inhibitors In Vivo. J Bone Miner Res. 2015;30:1822-30 pubmed publisher
    ..thought to exert their effects by providing resistance to binding/inhibition of secreted LRP5 inhibitors such as sclerostin (SOST) and Dickkopf homolog-1 (DKK1)...
  58. Naka T, Yokose S. Spatiotemporal expression of sclerostin in odontoblasts during embryonic mouse tooth morphogenesis. J Endod. 2011;37:340-5 pubmed publisher
    b>Sclerostin is the product of the SOST gene. Loss-of-function mutations in the SOST gene result in a high bone mass phenotype, thus confirming that sclerostin is a negative regulator of bone mass...
  59. Eda H, Santo L, Wein M, Hu D, Cirstea D, Nemani N, et al. Regulation of Sclerostin Expression in Multiple Myeloma by Dkk-1: A Potential Therapeutic Strategy for Myeloma Bone Disease. J Bone Miner Res. 2016;31:1225-34 pubmed publisher
    b>Sclerostin is a potent inhibitor of osteoblastogenesis. Interestingly, newly diagnosed multiple myeloma (MM) patients have high levels of circulating sclerostin that correlate with disease stage and fractures...
  60. Niziolek P, Farmer T, Cui Y, Turner C, Warman M, Robling A. High-bone-mass-producing mutations in the Wnt signaling pathway result in distinct skeletal phenotypes. Bone. 2011;49:1010-9 pubmed publisher
    ..to impart the HBM phenotype, in part, by increasing resistance to soluble Wnt signaling inhibitors, including sclerostin. Sost loss-of-function mutant mice (Sost knock-out) and Lrp5 gain-of-function mutant mice (Lrp5 HBM knock-in) ..
  61. Masuki H, Li M, Hasegawa T, Suzuki R, Ying G, Zhusheng L, et al. Immunolocalization of DMP1 and sclerostin in the epiphyseal trabecule and diaphyseal cortical bone of osteoprotegerin deficient mice. Biomed Res. 2010;31:307-18 pubmed
    ..lacunar-canalicular system (OLCS) and osteocyte-secreting molecules--dentin matrix protein (DMP) 1 and sclerostin--in the epiphyses and cortical bones of osteoprotegerin deficient (OPG(-/-)) mice...
  62. Kim B, Bae S, Lee S, Lee Y, Baek J, Park S, et al. TNF-? mediates the stimulation of sclerostin expression in an estrogen-deficient condition. Biochem Biophys Res Commun. 2012;424:170-5 pubmed publisher
    Although recent clinical studies have suggested a possible role for sclerostin, a secreted Wnt antagonist, in the pathogenesis of postmenopausal osteoporosis, the detailed mechanisms how estrogen deficiency regulates sclerostin expression ..
  63. Ryan Z, Ketha H, McNulty M, MCGEE LAWRENCE M, Craig T, Grande J, et al. Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium. Proc Natl Acad Sci U S A. 2013;110:6199-204 pubmed publisher
    Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton...
  64. Kuchler U, Schwarze U, Dobsak T, Heimel P, Bosshardt D, Kneissel M, et al. Dental and periodontal phenotype in sclerostin knockout mice. Int J Oral Sci. 2014;6:70-6 pubmed publisher
    b>Sclerostin is a Wnt signalling antagonist that controls bone metabolism. Sclerostin is expressed by osteocytes and cementocytes; however, its role in the formation of dental structures remains unclear...
  65. Fulzele K, Lai F, Dedic C, Saini V, Uda Y, Shi C, et al. Osteocyte-Secreted Wnt Signaling Inhibitor Sclerostin Contributes to Beige Adipogenesis in Peripheral Fat Depots. J Bone Miner Res. 2017;32:373-384 pubmed publisher
    ..Osteocytes, the most abundant bone cells, secrete a Wnt-signaling inhibitor called sclerostin. Here we examined three mouse models expressing high sclerostin levels, achieved through constitutive or ..
  66. Mosey H, Núñez J, Goring A, Clarkin C, Staines K, Lee P, et al. Sost Deficiency does not Alter Bone's Lacunar or Vascular Porosity in Mice. Front Mater. 2017;4:27 pubmed publisher
    b>SCLEROSTIN (Sost) is expressed predominantly in osteocytes acting as a negative regulator of bone formation...
  67. Tsourdi E, Rijntjes E, Köhrle J, Hofbauer L, Rauner M. Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1. Endocrinology. 2015;156:3517-27 pubmed publisher
    ..Here we tested whether hyperthyroidism and hypothyroidism interfere with dickkopf-1 (DKK1) and sclerostin, two inhibitors of Wnt signaling...
  68. Fontani F, Marcucci G, Iantomasi T, Brandi M, Vincenzini M. Glutathione, N-acetylcysteine and lipoic acid down-regulate starvation-induced apoptosis, RANKL/OPG ratio and sclerostin in osteocytes: involvement of JNK and ERK1/2 signalling. Calcif Tissue Int. 2015;96:335-46 pubmed publisher
    ..involved in bone remodelling such as the receptor activator kB ligand (RANKL), osteoprotegerin (OPG) and sclerostin. For this study, apoptosis was induced by serum starvation in a murine osteocyte-like cell line MLO-Y4; this ..
  69. Boschert V, Van Dinther M, Weidauer S, van Pee K, Muth E, Ten Dijke P, et al. Mutational analysis of sclerostin shows importance of the flexible loop and the cystine-knot for Wnt-signaling inhibition. PLoS ONE. 2013;8:e81710 pubmed publisher
    The cystine-knot containing protein Sclerostin is an important negative regulator of bone growth and therefore represents a promising therapeutic target...
  70. Kogawa M, Wijenayaka A, Ormsby R, Thomas G, Anderson P, Bonewald L, et al. Sclerostin regulates release of bone mineral by osteocytes by induction of carbonic anhydrase 2. J Bone Miner Res. 2013;28:2436-48 pubmed publisher
    The osteocyte product sclerostin is emerging as an important paracrine regulator of bone mass...
  71. Yang X, Han X, Shu R, Jiang F, Xu L, Xue C, et al. Effect of sclerostin removal in vivo on experimental periodontitis in mice. J Oral Sci. 2016;58:271-6 pubmed publisher
    We explored the effects of sclerostin removal in vivo on experimental periodontitis in mice...
  72. McGee Lawrence M, Ryan Z, Carpio L, Kakar S, Westendorf J, Kumar R. Sclerostin deficient mice rapidly heal bone defects by activating ?-catenin and increasing intramembranous ossification. Biochem Biophys Res Commun. 2013;441:886-90 pubmed publisher
    We investigated the influence of the osteocyte protein, sclerostin, on fracture healing by examining the dynamics and mechanisms of repair of single-cortex, stabilized femoral defects in sclerostin knockout (Sost(-/-); KO) and sclerostin ..
  73. Lehnen S, Gotz W, Baxmann M, Jager A. Immunohistochemical evidence for sclerostin during cementogenesis in mice. Ann Anat. 2012;194:415-21 pubmed publisher
    The purpose of this study was to investigate systematically the expression of the glycoprotein sclerostin, the product of the SOST gene, in periodontal tissues, especially in the cementum of mice...
  74. Paik J, Ding Z, Narurkar R, Ramkissoon S, Muller F, Kamoun W, et al. FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis. Cell Stem Cell. 2009;5:540-53 pubmed publisher
    ..Thus, the FoxO family coordinately regulates diverse genes and pathways to govern key aspects of NSC homeostasis in the mammalian brain. ..
  75. St John H, Hansen S, Pike J. Analysis of SOST expression using large minigenes reveals the MEF2C binding site in the evolutionarily conserved region (ECR5) enhancer mediates forskolin, but not 1,25-dihydroxyvitamin D3 or TGFβ1 responsiveness. J Steroid Biochem Mol Biol. 2016;164:277-280 pubmed publisher
    Transcribed from the SOST gene, sclerostin is an osteocyte-derived negative regulator of bone formation that inhibits osteoblastogenesis via antagonism of the Wnt pathway...
  76. Krishna S, Seto S, Jose R, Li J, Morton S, Biros E, et al. Wnt Signaling Pathway Inhibitor Sclerostin Inhibits Angiotensin II-Induced Aortic Aneurysm and Atherosclerosis. Arterioscler Thromb Vasc Biol. 2017;37:553-566 pubmed publisher
    b>Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease...
  77. Fairfield H, Falank C, Harris E, DeMambro V, McDonald M, Pettitt J, et al. The skeletal cell-derived molecule sclerostin drives bone marrow adipogenesis. J Cell Physiol. 2018;233:1156-1167 pubmed publisher
    ..Specifically, we found that physiologically relevant levels of Sclerostin (SOST), which is a Wnt-inhibitory molecule secreted from bone matrix-embedded osteocytes, can induce ..
  78. Kaesler N, Verhulst A, De Maré A, Deck A, Behets G, Hyusein A, et al. Sclerostin deficiency modifies the development of CKD-MBD in mice. Bone. 2018;107:115-123 pubmed publisher
    b>Sclerostin is a soluble antagonist of canonical Wnt signaling and a strong inhibitor of bone formation. We present experimental data on the role of sclerostin in chronic kidney disease - bone mineral disorder (CKD-MBD)...