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Sclerostin:一个新的骨形态发生蛋白抑制物 被引量：4

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摘要 SOST是新近发现的基因,该基因突变可导致其编码蛋白Sclerostin的异常表达,引起严重的骨代谢性疾病———Sclerosteosis和Van Buchem病。Sclerostin作为骨形态发生蛋白(BMP)的抑制物,通过竞争性与BMP受体结合,下调BMP的活性而抑制成骨,并通过与核结合因子α1(Cbfα1)和osterix(Osx)之间的相互作用,协调骨代谢过程。由于Sclerostin抑制骨形成,今后有望成为骨质疏松的治疗靶点。
作者 宋利格 张秀珍
机构地区 同济大学附属同济医院内分泌科
出处 《国外医学（内分泌学分册）》 2005年第5期319-321,共3页 Foreign Medical Sciences(Section of Endocrinology)
基金 国家自然科学基金资助项目(30070357)
关键词 骨质疏松 骨形态发生蛋白 SCLEROSTIN 抑制物 骨代谢性疾病 基因突变 异常表达 编码蛋白 受体结合 相互作用
分类号 R58 [医药卫生—内分泌]
  • 相关文献

参考文献18

  • 1Balemans W, Ebeling M, Patel N, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST).Hum Mol Genet,2001,10:537-543.
  • 2Hamersma H, Gardner J, Beighton P. The natural history of sclerosteosis.Clin Genet,2003,63:192-197.
  • 3Brunkow ME, Gardner JC, Van Ness J, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet,2001,68:577-589.
  • 4Kusu N, Laurikkala J, Imanishi M, et al. Sclerostin is a novel secreted osteoclast-derived bone morphogenetic protein antagonist with unique ligand specificity. J Biol Chem, 2003 , 278 : 24113-24117 .
  • 5Winkler DG, Sutherland MK, Geoghegan JC, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J,2003,22: 6267-6276.
  • 6Van Bezooijen RL, Roelen BA, Visser A, et al. Sclerostin is an osteocyteexpressed negative regulator of bone formation,but not a classical BMP antagonist. J Exp Med,2004,199:805-814.
  • 7Balemans W, Patel N, Ebeling M, et al. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet, 2002,39: 91-97.
  • 8Staehling-Hampton K, Proll S, Paeper BW, et al. A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet,2002,110:144-152.
  • 9Avsian-Kretchmer O, Hsueh AJ. Comparative genomic analysis of the eight-membered ring cystine knot-containing bone morphogenetic protein antagonists. Mol Endocrinol, 2004,18:1 - 12.
  • 10Laurikkala J,Kassai Y,Pakkasjarvi L, et al. Identification of a secreted BMP antagonist, ectodin, integrating BMP, FGF, and SHH signals from the tooth enamel knot. Dev Biol,2003,264:91-105.

同被引文献46

  • 1张智海,沈建雄,刘忠厚.中国人骨质疏松症诊断标准回顾性研究[J].中国骨质疏松杂志,2004,10(3):255-262. 被引量：110
  • 2Zofková I,Zajícková K,Hill M.The estrogen receptor alpha gene determines serum androstenedione levels in postmenopausal women[J].Steroids,2002,67(10):815-9.
  • 3Dierick H,Bejsovec A.Cellular mechanisms of Wingless/Wnt signal transduction[J].Curr Top Dev Biol,1999,43:153-190.
  • 4Liu T,DeCostanzo AJ,Liu X,et al.G protein signaling from activated rat frizzled-1 to the beta-catenin-Lef-Tcf pathway[J].Science,2001,292:1718-1722.
  • 5Nelson WJ,Nusse R.Convergence of Wnt/β-catenin and cadherinpathways[J].Science,2004,303(5663):1483-1487.
  • 6Yochum GS,Sherrick CM,Macpartlin M,et al.A beta-catenin/TCF-coordinated chromatin loop at MYC integrates 5' and 3' Wnt responsive enhancers[J].Proc Natl Acad Sci USA,2010,107(1):145-50.
  • 7Nelson WJ,Nusse R.Convergence of Wnt/β-catenin and cadherinpathways[J].Science,2004.303(5663):1483-1487.
  • 8Smith G, Stassen L, Flint S. Treating osteoporosis [J]. Ir Med J, 2009, 102(3):88.
  • 9Hansjoerg Keller, Michaela Kneissel. SOST is a target gene for PTH in bone [J]. Bone,2005, 37:148-158.
  • 10Ellies DL, Viviano B, McCarthy J, et al. Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity[J]. J Bone Miner Res, 2006, 21 (11):1738-49.

引证文献4

二级引证文献19

国外医学（内分泌学分册）
2005年 第5期

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