郭清河;叶添文;

• 1:第二军医大学附属长征医院骨科

摘要(Abstract)：

<正>骨质疏松是一种严重的老年性疾病。全球骨质疏松的患者约2亿人。在中国,骨质疏松的患者超过9 000万,约占总人口的7.1%。骨质疏松症及其引起的骨折位居常见疾病的第7位,严重威胁着中、老年人的健康,成为全球公共卫生问题之一。骨质疏松与成骨细胞/破骨细胞功能障碍有关。影响成骨细胞/破骨细胞增殖、分化及功能的各种因素是骨质疏松发病的重要原因。在上皮组织中高度表达的钙离子通道TRPV5/TRPV6,对全身钙离子代谢有着非常重要的作用。认识骨组织代谢调控因子TRPV5/TRPV6在骨质疏松发病机制中的作用,

关键词(KeyWords)： 钙离子通道;TRPV;骨质疏松

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(编号30801172);; 上海市科学技术委员会资助项目(编号10411963500)

作者(Author): 郭清河;叶添文;

Email:

DOI:

参考文献(References)：

• [1]Hoenderop JG,van der Kemp AW,Hartog A,et al.Molecular identi-fication of the apical Ca2+channel in 1,25-dihydroxyvitamin D3 re-sponsive epithelia[J].J Biol Chem,1999,274:8375-8378.
• [2]Schoeber JP,Hoenderop JG,Bindels RJ.Concerted action of associ-ated proteins in the regulation of TRPV5 and TRPV6[J].J BiochemSoc Trans,2007,35:115-119.
• [3]Hoenderop JG,Vennekens R,Muller D,et al.Function and expres-sion of the epithelial Ca(2+)channel family:comparison of mamma-lian ECaC1 and 2[J].J Physiol,2001,537:747-761.
• [4]Nijenhuis T,Hoenderop JG,van-der-Kemp AW,et al.Localiza-tion and regulation of the epithelial Ca2+channel TRPV6 in the kid-ney[J].J Am Soc Nephrol,2003,14:2731-2740.
• [5]van de Graaf SF,Boullart L,Hoenderop JG,et al.Regulation of theepithelial Ca2+channels TRPV5 and TRPV6 by 1alpha,25-di-hydroxy vitamin D3 and dietary Ca2+[J].J Steroid Biochem Mol Bi-ol,2004,89-90:303-308.
• [6]Topala CN,Schoeber JP,Searchfield LE,et al.Activation of the Ca2+-sensing receptor stimulates the activity of the epithelial Ca2+channel TRPV5[J].J Cell Calcium,2009,45:331-339.
• [7]Lee KP,Nair AV,Grimm C,et al.A helix-breaking mutation inthe epithelial Ca(2+)channel TRPV5 leads to reduced Ca(2+)-dependent inactivation[J].J Cell Calcium,2010,48:275-287.
• [8]Hoenderop JG,Nilius B,Bindels RJ.Calcium absorption across epithe-lia[J].J Physiol Rev,2005,85:373-422.
• [9]Hoenderop JG,Muller D,Van Der Kemp AW,et al.Calcitriol controlsthe epithelial calcium channel in kidney[J].J Am Soc Nephrol,2001,12:1342-1349.
• [10]Ko SH,Choi KC,Oh GT,et al.Effect of dietary calcium and1,25-(OH)2D3 on the expression of calcium transport genes in calbindin-D9k and-D28k double knockout mice[J].J Biochem Biophys ResCommun,2009,379:227-232.
• [11]Christakos S,Dhawan P,Ajibade D,et al.Mechanisms involved in vita-min D mediated intestinal calcium absorption and in non-classical ac-tions of vitamin D[J].J Steroid Biochem Mol Biol,2010,121:183-187.
• [12]Hoenderop JG,Hartog A,Stuiver M,et al.Localization of the epithe-lial Ca(2+)channel in rabbit kidney and intestine[J].J Am SocNephrol,2000,11:1171-1178.
• [13]Hoenderop JG,Bindels RJ.Calciotropic and magnesiotropic TRP chan-nels[J].J Physiology(Bethesda),2008,23:32-40.
• [14]van der Eerden BC,Hoenderop JG,de Vries TJ,et al.The epithelialCa2+channel TRPV5 is essential for proper osteoclastic bone resorp-tion[J].J Proc Natl Acad Sci USA,2005,102:17507-17512.
• [15]Muller D,Hoenderop JG,Merkx GF,et al.Gene structure and chromo-somal mapping of human epithelial calcium channel[J].J BiochemBiophys Res Commun,2000,18:47-52.
• [16]Weber K,Erben RG,Rump A,et al.Gene structure and regulationof the murine epithelial calcium channels ECaC1 and 2[J].J Bio-chem Biophys Res Commun,2001,289:1287-1294.
• [17]Benn BS,Ajibade D,Porta A,et al.Active intestinal calcium trans-port in the absence of transient receptor potential vanilloid type 6 andcalbindin-D9k[J].J Endocrinology,2008,149:3196-3205.
• [18]Lieben L,Benn BS,Ajibade D,et al.Trpv6mediates intestinal cal-cium absorption during calcium restriction and contributes to bone ho-meostasis[J].Bone,2010,47:301-308.
• [19]Thyagarajan B,Benn BS,Christakos S,et al.Phospholipase C-me-diated regulation of transient receptor potential vanilloid 6 channels:implications in active intestinal Ca2+transport[J].J Mol Pharma-col,2009,75:608-616.
• [20]Bary EL.Expression of mRNA for the alpha1subunit of voltage-ga-ted calcium channels in human osteoblast-like cell lines and normalhuman osteoblasts[J].J Calcif Tissue Int,2000,66:145-150.
• [21]Barthel TK,Mathern DR,Whitfield GK,et al.1,25-DihydroxyvitaminD3/VDR-mediated induction of FGF23 as well as transcriptionalcontrol of other bone anabolic and catabolic genes that orchestrate theregulation of phosphate and calcium mineral metabolism[J].J SteroidBiochem Mol Biol,2007,103:381-388.
• [22]Bianco SD,Peng JB,Takanaga H,et al.Marked disturbance of calci-um homeostasis in mice with targeted disruption of the Trpv6 calciumchannel gene[J].J Bone Miner Res,2007,22:274-85.
• [23]Huybers S,Naber TH,Bindels RJ,et al.Prednisolone-induced Ca2+malabsorption is caused by diminished expression of the epithelialCa2+channel TRPV6[J].J Physiol Gastrointest Liver Physiol,2007,292:92-97.
• [24]Van Cromphaut SJ,Stockmans I,Torrekens S,et al.Duodenal calci-um absorption in dexamethasone-treated mice:functional and molec-ular aspects[J].J Arch Biochem Biophys,2007,460:300-305.
• [25]Kim MH,Lee GS,Jung EM,et al.The negative effect of dexametha-sone on calcium-processing gene expressions is associated with a glu-cocorticoid-induced calcium-absorbing disorder[J].J Life Sci,2009,85:146-152.
• [26]Walters JR,Balesaria S,Chavele KM,et al.Calcium channel TRPV6expression in human duodenum:different relationships to the vitaminD system and aging in men and women[J].J Bone Miner Res,2006,21:1770-1777.
• [27]Irnaten M,Blanchard-Gutton N,Harvey BJ.Rapid effects of17beta-estradiol on epithelial TRPV6 Ca2+channel in human T84 coloniccells[J].J Cell Calcium,2008,44:441-452.
• [28]Bianco SD,Peng JB,Takanaga H,et al.Marked disturbance of calci-um homeostasis in mice with targeted disruption of the Trpv6 calciumchannel gene[J].J Bone Miner Res,2007,22:274-285.
• [29]Peng JB,Zhuang L,Berger UV,et al.CaT1expression correlates withtumor grade in prostate cancer[J].J Biochem Biophys Res Commun,2001,282:729-734.
• [30]Chwarz EC,Wissenbach U,Niemeyer BA,et al.TRPV6potentiatescalcium-dependent cell proliferation[J].J Cell Calcium,2006,39:163-173.