骨硬化蛋白与DKK1蛋白在慢性肾脏病-矿物质骨代谢紊乱中的研究进展
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摘要
慢性肾脏病-矿物质骨代谢紊乱(chronic kidney disease-mineral and bone disorder, CKD-MBD)是慢性肾脏病(chronic kidney disease, CKD)患者的常见并发症,对其发病机制的研究目前认为主要与钙磷代谢异常以及甲状旁腺素(parathyroid hormone, PTH)、维生素D有关,但这些标记物一般在CKD的后期才出现明显改变。国内外实验研究表明,骨硬化蛋白(Sclerostin)与DKK-1蛋白作为Wnt信号通路的抑制剂参与了CKD-MBD的发病过程,对CKD-MBD的发病机制及诊疗有着重要意义。因此本文从骨硬化蛋白与DKK1蛋白着手对其在CKD-MBD中的作用及意义做一综述,以期对CKD-MBD的发病机制有更深的了解并为其治疗提供新的思路与方法。
引文
[1]Zhang L,Wang F,Wang L,et al.中国慢性肾脏病的流行病学调查:横断面研究[J].中华肾病研究电子杂志,2012,1(02):127.
[2]KDIQO.KDIQO 2012 clinical practice guideline for the eveluation and management of chronic kidney disease[J].Kidney Int Suppl,2013,3(1):1-150.
[3]Kidney Disease:Improving Global Outcomes(KDIGO)CKD-MBD Work Group.KDIGO clinical practice guideline for the diagnosis,evaluation,prevention,and treatment of Chronic Kidney Disease-Mineral and Bone Disorder(CKD-MBD).Kidney Int Suppl,2009,113(suppl):S1-130.
[4]Costa AG,Bilezikian JP,Lewiecki EM.The potential use of anti sclerostin therapy in chronic kidney disease-mineral and bone disorder[J].Curr Opin Nephrol Hypertension,2015,24(4):324-329.
[5]Moysés R M,Schiavi S C.Sclerostin,Osteocytes,and Chronic Kidney Disease-Mineral Bone Disorder[J].Seminars Dialysis,2015,28(6):578-586.
[6]Cejka D,J?ger-Lansky A,Kieweg H,et al.Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients[J].Nephrol Dial Transplant,2012,27(1):226-30.
[7]van Bezooijen RL,Ten DP,Papapoulos SE,et al.SOST/sclerostin,an osteocyte-derived negative regulator of bone formation.[J].Cytokine Growth Factor Reviews,2005,16(3):319-27.
[8]张爽,高艳虹.Sclerostin在骨代谢中的作用和机制[J].上海交通大学学报(医学版),2015,35(4):589-593.
[9]Wu W,Glinka A,Delius H,et al.Mutual antagonism between dickkopf1 and dickkopf2 regulates Wnt/beta-catenin signalling.[J].Current Biology Cb,2000,10(24):1611.
[10]王凡,黄宏兴,王吉利,等.补肾健脾活血方干预过表达DKK1骨细胞对细胞活性及BMP2的影响[J].中国骨质疏松杂志,2017,23(6):711-714.
[11]Zhang Z,Iglesias DM,Corsini R,et al.WNT/β-Catenin Signaling is Required for Integration of CD24+Renal Progenitor Cells into Glycerol-Damaged Adult Renal Tubules.[J].Stem Cells Int,2015,2015:1-11.
[12]王强,舒冰,赵永见,等.Wnt/β-catenin信号通路与肾性骨病[J].中国骨质疏松杂志,2016,22(12):1618-1622.
[13]Kim W,Kim M,Jho EH.Wnt/β-catenin signalling:from plasma membrane to nucleus.[J].Biochem J,2013,450(1):9.
[14]Baron R,Kneissel M.WNT signaling in bone homeostasis and disease:from human mutations to treatments.[J].Nature Med,2013,19(2):179-192.
[15]Pelletier S,Dubourg L,Carlier M C,et al.The relation between renal function and serum sclerostin in adult patients with CKD.[J].Clin J Am Society Nephrol Cjasn,2013,8(5):819.
[16]Cejka D,Marculescu R,Kozakowski N,et al.Renal elimination of sclerostin increases with declining kidney function.[J].J Clin Endocrinol Metab,2014,99(1):248-255.
[17]Yamada S,Tsuruya K,Tokumoto M,et al.Factors associated with serum soluble inhibitors of Wnt-β-catenin signaling(sclerostin and dickkopf-1)in patients undergoing peritoneal dialysis[J].Nephrology,2015,20(9):639-645.
[18]Behets G J,Viaene L,Meijers B,et al.Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD:[J].Plos One,2017,12(5):e0176411.
[19]Noordzij M,Cranenburg E M,Engelsman L F,et al.Progression of aortic calcification is associated with disorders of mineral metabolism and mortality in chronic dialysis patients[J].Nephrology,dialysis,transplantation:official publication of the European Dialysis and Transplant Association-European Renal Association,2011,26(5):1662.
[20]李怀鱼,杨军,王振兴,等.血液透析患者血清中骨硬化蛋白和DKK1蛋白表达与腹主动脉钙化程度的相关性分析[J].中国药物与临床,2017,17(1):79-81.
[21]Kramann R,Brandenburg V M,Schurgers L J,et al.Novel insights into osteogenesis and matrix remodelling associated with calcific uraemic arteriolopathy.[J].Nephrol Dial Transplant,2013,28(4):856-868.
[22]Brandenburg V M,Kramann R,Koos R,et al.Relationship between sclerostin and cardiovascular calcification in hemodialysis patients:a cross-sectional study[J].BMC Nephrol,2013,14(1):219.
[23]Morena M,Jaussent I,Dupuy A M,et al.Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis:potential partners in vascular calcifications[J].Nephrology,dialysis,transplantation:official publication of the European Dialysis and Transplant Association-European Renal Association,2015,30(8):1345-1356.
[24]Lee YT,Ng HY,Chiu TT,et al.Association of bone-derived biomarkers with vascular calcification in chronic hemodialysis patients.[J].Clin Chim Acta,2016,452:38-43.
[25]Claes KJ,Viaene L,Heye S,et al.Sclerostin:Another vascular calcification inhibitor[J].J Clin Endocrinol Metab,2013,98(8):3221-3228.
[26]周华,崔笠,杨敏,等.慢性肾脏病5期患者sclerostin与桡动脉钙化的关系[J].临床荟萃,2015,30(6):645-648.
[27]Thambiah S,Roplekar R,Manghat P,et al.Circulating Sclerostin and Dickkopf-1(DKK1)in Predialysis Chronic Kidney Disease(CKD):Relationship with Bone Density and Arterial Stiffness[J].Calcif Tissue Int,2012,90(6):473-480.
[28]Rodda S J,Mcmahon A P.Distinct roles for Hedgehog and canonical Wnt signaling in specification,differentiation and maintenance of osteoblast progenitors.[J].Development,2006,133(16):3231-3244.
[29]Wei W,Zeve D,Suh JM,et al.Biphasic and Dosage-Dependent Regulation of Osteoclastogenesis byβ-Catenin[J].Molecul Cell Biol,2011,48(23):4706-4719.
[30]Ryan ZC,Ketha H,Mcnulty MS,et al.Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23concentrations and the urinary excretion of calcium[J].Proc Natl Acad Sci USA,2013,110(15):6199-6204.
[31]Moe SM,Chen NX,Newman CL,et al.Anti-Sclerostin Antibody Treatment in a Rat Model of Progressive Renal Osteodystrophy.[J].J Bone Mine Res,2015,30(3):539-549.
[32]Fang Y,Ginsberg C,Seifert M,et al.CKD-induced wingless/integration 1 inhibitors and phosphorus cause the CKD-mineral and bone disorder[J].J Am Society Nephrol Jasn,2014,25(8):1760.
[2]KDIQO.KDIQO 2012 clinical practice guideline for the eveluation and management of chronic kidney disease[J].Kidney Int Suppl,2013,3(1):1-150.
[3]Kidney Disease:Improving Global Outcomes(KDIGO)CKD-MBD Work Group.KDIGO clinical practice guideline for the diagnosis,evaluation,prevention,and treatment of Chronic Kidney Disease-Mineral and Bone Disorder(CKD-MBD).Kidney Int Suppl,2009,113(suppl):S1-130.
[4]Costa AG,Bilezikian JP,Lewiecki EM.The potential use of anti sclerostin therapy in chronic kidney disease-mineral and bone disorder[J].Curr Opin Nephrol Hypertension,2015,24(4):324-329.
[5]Moysés R M,Schiavi S C.Sclerostin,Osteocytes,and Chronic Kidney Disease-Mineral Bone Disorder[J].Seminars Dialysis,2015,28(6):578-586.
[6]Cejka D,J?ger-Lansky A,Kieweg H,et al.Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients[J].Nephrol Dial Transplant,2012,27(1):226-30.
[7]van Bezooijen RL,Ten DP,Papapoulos SE,et al.SOST/sclerostin,an osteocyte-derived negative regulator of bone formation.[J].Cytokine Growth Factor Reviews,2005,16(3):319-27.
[8]张爽,高艳虹.Sclerostin在骨代谢中的作用和机制[J].上海交通大学学报(医学版),2015,35(4):589-593.
[9]Wu W,Glinka A,Delius H,et al.Mutual antagonism between dickkopf1 and dickkopf2 regulates Wnt/beta-catenin signalling.[J].Current Biology Cb,2000,10(24):1611.
[10]王凡,黄宏兴,王吉利,等.补肾健脾活血方干预过表达DKK1骨细胞对细胞活性及BMP2的影响[J].中国骨质疏松杂志,2017,23(6):711-714.
[11]Zhang Z,Iglesias DM,Corsini R,et al.WNT/β-Catenin Signaling is Required for Integration of CD24+Renal Progenitor Cells into Glycerol-Damaged Adult Renal Tubules.[J].Stem Cells Int,2015,2015:1-11.
[12]王强,舒冰,赵永见,等.Wnt/β-catenin信号通路与肾性骨病[J].中国骨质疏松杂志,2016,22(12):1618-1622.
[13]Kim W,Kim M,Jho EH.Wnt/β-catenin signalling:from plasma membrane to nucleus.[J].Biochem J,2013,450(1):9.
[14]Baron R,Kneissel M.WNT signaling in bone homeostasis and disease:from human mutations to treatments.[J].Nature Med,2013,19(2):179-192.
[15]Pelletier S,Dubourg L,Carlier M C,et al.The relation between renal function and serum sclerostin in adult patients with CKD.[J].Clin J Am Society Nephrol Cjasn,2013,8(5):819.
[16]Cejka D,Marculescu R,Kozakowski N,et al.Renal elimination of sclerostin increases with declining kidney function.[J].J Clin Endocrinol Metab,2014,99(1):248-255.
[17]Yamada S,Tsuruya K,Tokumoto M,et al.Factors associated with serum soluble inhibitors of Wnt-β-catenin signaling(sclerostin and dickkopf-1)in patients undergoing peritoneal dialysis[J].Nephrology,2015,20(9):639-645.
[18]Behets G J,Viaene L,Meijers B,et al.Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD:[J].Plos One,2017,12(5):e0176411.
[19]Noordzij M,Cranenburg E M,Engelsman L F,et al.Progression of aortic calcification is associated with disorders of mineral metabolism and mortality in chronic dialysis patients[J].Nephrology,dialysis,transplantation:official publication of the European Dialysis and Transplant Association-European Renal Association,2011,26(5):1662.
[20]李怀鱼,杨军,王振兴,等.血液透析患者血清中骨硬化蛋白和DKK1蛋白表达与腹主动脉钙化程度的相关性分析[J].中国药物与临床,2017,17(1):79-81.
[21]Kramann R,Brandenburg V M,Schurgers L J,et al.Novel insights into osteogenesis and matrix remodelling associated with calcific uraemic arteriolopathy.[J].Nephrol Dial Transplant,2013,28(4):856-868.
[22]Brandenburg V M,Kramann R,Koos R,et al.Relationship between sclerostin and cardiovascular calcification in hemodialysis patients:a cross-sectional study[J].BMC Nephrol,2013,14(1):219.
[23]Morena M,Jaussent I,Dupuy A M,et al.Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis:potential partners in vascular calcifications[J].Nephrology,dialysis,transplantation:official publication of the European Dialysis and Transplant Association-European Renal Association,2015,30(8):1345-1356.
[24]Lee YT,Ng HY,Chiu TT,et al.Association of bone-derived biomarkers with vascular calcification in chronic hemodialysis patients.[J].Clin Chim Acta,2016,452:38-43.
[25]Claes KJ,Viaene L,Heye S,et al.Sclerostin:Another vascular calcification inhibitor[J].J Clin Endocrinol Metab,2013,98(8):3221-3228.
[26]周华,崔笠,杨敏,等.慢性肾脏病5期患者sclerostin与桡动脉钙化的关系[J].临床荟萃,2015,30(6):645-648.
[27]Thambiah S,Roplekar R,Manghat P,et al.Circulating Sclerostin and Dickkopf-1(DKK1)in Predialysis Chronic Kidney Disease(CKD):Relationship with Bone Density and Arterial Stiffness[J].Calcif Tissue Int,2012,90(6):473-480.
[28]Rodda S J,Mcmahon A P.Distinct roles for Hedgehog and canonical Wnt signaling in specification,differentiation and maintenance of osteoblast progenitors.[J].Development,2006,133(16):3231-3244.
[29]Wei W,Zeve D,Suh JM,et al.Biphasic and Dosage-Dependent Regulation of Osteoclastogenesis byβ-Catenin[J].Molecul Cell Biol,2011,48(23):4706-4719.
[30]Ryan ZC,Ketha H,Mcnulty MS,et al.Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23concentrations and the urinary excretion of calcium[J].Proc Natl Acad Sci USA,2013,110(15):6199-6204.
[31]Moe SM,Chen NX,Newman CL,et al.Anti-Sclerostin Antibody Treatment in a Rat Model of Progressive Renal Osteodystrophy.[J].J Bone Mine Res,2015,30(3):539-549.
[32]Fang Y,Ginsberg C,Seifert M,et al.CKD-induced wingless/integration 1 inhibitors and phosphorus cause the CKD-mineral and bone disorder[J].J Am Society Nephrol Jasn,2014,25(8):1760.