BMP/Smads信号通路与强直性脊柱炎病理成骨的研究进展
摘要
骨形态生成蛋白(bone morphogenetic protein,BMP)/Smads信号传导通路目前被认为是强直性脊柱炎(ankylosing spondylitis,AS)病理成骨的一条重要途径。BMP通过激活Smads蛋白将转化生长因子-β(transforming growth factor-β,TGF-β)信号由细胞膜转至细胞核,诱导核内成骨基因表达,使组织纤维化、骨化。一些介质蛋白对BMP/Smads信号传导通路具有抑制作用,可为治疗AS病理成骨提供新的靶点。本文就BMP/Smads信号传导通路与AS病理性成骨的相关研究作一综述。
引文
[1]雷鹏真,危国军,裴孝鹏,等.Dickkopf-1在强直性脊柱炎病理过程中作用研究进展[J].中华实用诊断与治疗杂志,2012,26(12):1149-1151.
[2]刘波.2种方法检测强直性脊柱炎患者HLA-B27的应用比较[J].中华全科医学,2012,10(5):789,812.
[3]Wiley D M,Jin S W.Bone morphogenetic protein functions as a context-dependent angiogenic cue in vertebrates[J].Semin Cell Dev Biol,2011,22(9):1012-1018.
[4]Sakou T,Onishi T,Yamamoto T,et al.Localization of Smads,the TGF-beta family intracellular signaling components during endochondral ossification[J].J Bone Miner Res,1999,14(7):1145-1152.
[5]Rath B,Nam J,Deschner J,et al.Biomechanical forces exert anabolic effects on osteoblasts by activation of Smad 1/5/8through type 1BMP receptor[J].Biorheology,2011,48(1):37-48.
[6]Callery E M,Park C Y,Xu X,et al.Eps15Ris required for bone morphogenetic protein signalling and differentially compartmentalizes with Smad proteins[J].Open Biology,2012,2(4):120060.
[7]Hariharan R,Pillai M R.Structure-function relationship of inhibitory Smads:structural flexibility contributes to functional divergence[J].Proteins,2008,71(4):1853-1862.
[8]Bonor J,Adams E L,Bragdon B,et al.Initiation of BMP2signaling in domains on the plasma membrane[J].J Cell Physiol,2012,227(7):2880-2888.
[9]明磊国,陈克明.骨形成过程中两条重要的信号转导通路[J].中国骨质疏松杂志,2011,17(3):275-278.
[10]Gandavarapu N R,Mariner P D,Schwartz M P,et al.Extracellular matrix protein adsorption to phosphatefunctionalized gels from serum promotes osteogenic differentiation of human mesenchymal stem cells[J].Acta Biomater,2013,9(1):4525-4534.
[11]Takano M,Otsuka F,Matsumoto Y,et al.Peroxisome proliferator-activated receptor activity is involved in the osteoblastic differentiation regulated by bone morphogenetic proteins and tumor necrosis factor-α[J].Mol Cell Endocrinol,2012,348(1):224-232.
[12]Lories R J,Derese I,Luyten F P.Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis[J].J Clin Invest,2005,115(6):1571-1579.
[13]王庆文,曾沛英,蔡月明,等.转化生长因子β1/结缔组织生长因子通路在强直性脊柱炎中的表达[J].北京大学学报:医学版,2012,44(2):244-249.
[14]Hyzy S L,Olivares-Navarrete R,Schwartz Z,et al.BMP-2induces osteoblast apoptosis in a maturation state and noggindependent manner[J].J Cell Biochem,2012,113(10):3236-3245.
[15]Chen C,Uludag H,Wang Z,et al.Noggin suppression decreases BMP-2-induced osteogenesis of human bone marrowderived mesenchymal stem cells in vitro[J].J Cell Biochem,2012,113(12):3672-3680.
[16]Xin H,Xu X,Li L,et al.CHIP controls the sensitivity of transforming growth factor-beta signaling by modulating the basal level of Smad-3through ubiquitin-mediated degradation[J].J Biol Chem,2005,280(21):20842-20850.
[17]Wang L,Liu Y T,Hao R,et al.Molecular mechanism of the negative regulation of Smad-1/5protein by carboxyl terminus of Hsc70-interacting protein(CHIP)[J].J Biol Chem,2011,286(18):15883-15894.
[18]Ka S M,Huang X R,Lan H Y,et al.Smad-7gene therapy ameliorates an autoimmune crescentic glomerulonephritis in mice[J].J Am Soc Nephrol,2007,18(6):1777-1788.
[19]Yano M,Inoue Y,Tobimatsu T,et al.Smad-7inhibits differentiation and mineralization of mouse osteoblastic cells[J].Endocr J,2012,59(8):653-662.
[2]刘波.2种方法检测强直性脊柱炎患者HLA-B27的应用比较[J].中华全科医学,2012,10(5):789,812.
[3]Wiley D M,Jin S W.Bone morphogenetic protein functions as a context-dependent angiogenic cue in vertebrates[J].Semin Cell Dev Biol,2011,22(9):1012-1018.
[4]Sakou T,Onishi T,Yamamoto T,et al.Localization of Smads,the TGF-beta family intracellular signaling components during endochondral ossification[J].J Bone Miner Res,1999,14(7):1145-1152.
[5]Rath B,Nam J,Deschner J,et al.Biomechanical forces exert anabolic effects on osteoblasts by activation of Smad 1/5/8through type 1BMP receptor[J].Biorheology,2011,48(1):37-48.
[6]Callery E M,Park C Y,Xu X,et al.Eps15Ris required for bone morphogenetic protein signalling and differentially compartmentalizes with Smad proteins[J].Open Biology,2012,2(4):120060.
[7]Hariharan R,Pillai M R.Structure-function relationship of inhibitory Smads:structural flexibility contributes to functional divergence[J].Proteins,2008,71(4):1853-1862.
[8]Bonor J,Adams E L,Bragdon B,et al.Initiation of BMP2signaling in domains on the plasma membrane[J].J Cell Physiol,2012,227(7):2880-2888.
[9]明磊国,陈克明.骨形成过程中两条重要的信号转导通路[J].中国骨质疏松杂志,2011,17(3):275-278.
[10]Gandavarapu N R,Mariner P D,Schwartz M P,et al.Extracellular matrix protein adsorption to phosphatefunctionalized gels from serum promotes osteogenic differentiation of human mesenchymal stem cells[J].Acta Biomater,2013,9(1):4525-4534.
[11]Takano M,Otsuka F,Matsumoto Y,et al.Peroxisome proliferator-activated receptor activity is involved in the osteoblastic differentiation regulated by bone morphogenetic proteins and tumor necrosis factor-α[J].Mol Cell Endocrinol,2012,348(1):224-232.
[12]Lories R J,Derese I,Luyten F P.Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis[J].J Clin Invest,2005,115(6):1571-1579.
[13]王庆文,曾沛英,蔡月明,等.转化生长因子β1/结缔组织生长因子通路在强直性脊柱炎中的表达[J].北京大学学报:医学版,2012,44(2):244-249.
[14]Hyzy S L,Olivares-Navarrete R,Schwartz Z,et al.BMP-2induces osteoblast apoptosis in a maturation state and noggindependent manner[J].J Cell Biochem,2012,113(10):3236-3245.
[15]Chen C,Uludag H,Wang Z,et al.Noggin suppression decreases BMP-2-induced osteogenesis of human bone marrowderived mesenchymal stem cells in vitro[J].J Cell Biochem,2012,113(12):3672-3680.
[16]Xin H,Xu X,Li L,et al.CHIP controls the sensitivity of transforming growth factor-beta signaling by modulating the basal level of Smad-3through ubiquitin-mediated degradation[J].J Biol Chem,2005,280(21):20842-20850.
[17]Wang L,Liu Y T,Hao R,et al.Molecular mechanism of the negative regulation of Smad-1/5protein by carboxyl terminus of Hsc70-interacting protein(CHIP)[J].J Biol Chem,2011,286(18):15883-15894.
[18]Ka S M,Huang X R,Lan H Y,et al.Smad-7gene therapy ameliorates an autoimmune crescentic glomerulonephritis in mice[J].J Am Soc Nephrol,2007,18(6):1777-1788.
[19]Yano M,Inoue Y,Tobimatsu T,et al.Smad-7inhibits differentiation and mineralization of mouse osteoblastic cells[J].Endocr J,2012,59(8):653-662.