Rab蛋白与骨质疏松症关系浅析
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摘要
随着人口老龄化进程的不断推进,骨质疏松症的发病率逐年升高。Rab蛋白作为一类具有特殊生物学活性的小分子蛋白,广泛存在于真核细胞中。骨髓间充质干细胞所分泌的外泌体可携带Rab蛋白,并能定向运输到靶标以发挥其独有的生物学作用,从而达到调控骨质疏松症发生、发展的目的。笔者基于近年来的国内外文献研究,总结Rab蛋白与骨质疏松症之间的联系,为骨质疏松症的防治提供新的研究方向。
With the continuous advancement of the aging process in the population, the incidence of osteoporosis is getting higher and higher. Rab protein is a kind of small molecule protein with special biological activity, which is widely expressed in eukaryotic cells. The exosomes secreted by bone marrow mesenchymal stem cells can carry Rab protein, and can transport it to the target to play its unique biological role, Resultsing in the regulation of the occurrence and development of osteoporosis. Based on recent national and international literature research, this article summarizes the link between Rab protein and osteoporosis and provides new research directions for the prevention and treatment of osteoporosis.
With the continuous advancement of the aging process in the population, the incidence of osteoporosis is getting higher and higher. Rab protein is a kind of small molecule protein with special biological activity, which is widely expressed in eukaryotic cells. The exosomes secreted by bone marrow mesenchymal stem cells can carry Rab protein, and can transport it to the target to play its unique biological role, Resultsing in the regulation of the occurrence and development of osteoporosis. Based on recent national and international literature research, this article summarizes the link between Rab protein and osteoporosis and provides new research directions for the prevention and treatment of osteoporosis.
引文
[1] 张智海,张智若,刘忠厚,等.中国大陆地区以-2.0SD为诊断标准的骨质疏松症发病率回顾性研究[J].中国骨质疏松杂志,2016,22(1):1-8.
[2] 鲁尚德.骨质疏松症病因病机研究概况[J].世界最新医学信息文摘,2016,16(38):44-45,51.
[3] Blanc L,Vidal M.New insights into the function of Rab GTPases in the context of exosomal secretion[J].Small GTPases.2018,9(1-2):95-106.
[4] 张岩.预防老年人骨质疏松[J].护士进修杂志,2010,25(3):195-197.
[5] Boivin G,Vedi S,Purdid DW,et al.Influence ofestrogen therapy Atconventional and high doses on the digree of mineralization of iliac bone tissue:a quantitativemicrora-diographic analysis in postmenopausalwomen[J].Bone,2005,36(3):562-567.
[6] 姚锦容,李彬强.1500例中老年妇女骨密度调查[J].社区医学杂志,2011,9(15):63-64.
[7] Bailey DA,McKay HA,Mirwald RL,et al.A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children:the university of Saskatchewan bone mineral accrual study[J].J Bone Miner Res.1999,14(10):1672-1679.
[8] Vuori IM.Dose-response of physical activity and low back pain,osteoarthritis,and osteoporosis[J].Med Sci Sports Exerc.2001,33(6 Suppl):S551-S586.
[9] 宋东伟,徐斌,王玉姝,等.选择性雌激素受体调节剂组织选择性作用研究进展[J].现代药物与临床,2014,29(2):206-210.
[10] Cervellati C,Bonaccorsi G,Cremonini E,et al.Oxidative stress and bone resorption interplay as a possible trigger for postmenopausal osteoporosis [J].Biomed Res Int,2014(2014):569563.
[11] 张晶,付勤.IL-17在绝经后骨质疏松方面的相关研究[J].中国骨质疏松杂志,2013,19(3):310-313.
[12] 杨剑.Rab3D蛋白促进肿瘤转移和Hsp90α质膜转运信号的研究[D].北京:清华大学,2015.
[13] Shimadal K,Uzawa K,Kato M,et al.Aberrant expression of RAB1A in human tongue cancer[J].Br J Cancer,2005,92(10):1915-1921.
[14] Croizet Berger K,Daumerie C,Couvreur M,et al.The endocytic catalysts,Rab5a and Rab7,are tandem regulators of thyroid hormone production[J].Proc Natl Acad Sci USA,2002,99(12):8277-8282.
[15] Calvo A,Xiao N,Kang J,et al.Alterations in gene expression profiles during prostate cancer progression:functional correlations to tumorigenicity and downregulation of selenoprotein-P in mouse and human tumors[J].Cancer Res,2002,62(18):5325-5335.
[16] Mor O,Nativ O,Stein A,et al.Molecular analysis of transitional cell carcinoma using c DNA microarray[J].Oncogene,2003,22(48):7702-7710.
[17] Wang W,Wyckoff JB,Frohlich VC,et al.Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling[J].Cancer Res,2002,62(21):6278-6288.
[18] Sorlie T,Tibshirani R,Parker J,et al.Repeated observation of breast tumor subtypes in independent gene expression data sets[J].Proc Natl Acad Sci USA,2003,100(14):8418-8123.
[19] Schaner ME,Ross DT,Ciaravino G,et al.Gene expression patterns in ovarian carcinomas[J].Mol Biol Cell,2003,14(11):4376-4386.
[20] Cha BH,Jung MJ,Moon BK,et al.Administration of taurour-sodeoxycholic acid enhances osteogenic differentiation of bone marrow derived mesenchymal stem cells and bone regeneration[J].Bone,2015(83):73-81.
[21] Li C,Wei G,Gu Q,et al.Donor Age and Cell Passage Affect Osteogenic Ability of Rat Bone Marrow Mesenchymal Stem Cells [J].Cell Biochemistry & Biophysics,2015,72(2):543-549.
[22] Itzstein C,Coxon FP,Rogers MJ.The regulation of osteoclast function and bone resorption by small GTPases[J].Small GTPases.2011,2(3):117-130.
[23] Pereira-Leal JB,Seabra MC.Evolution of the Rab family of small GTP-binding proteins[J].J Mol Biol,2001,313 (4):889-901.
[24] Barral DC,Ramalho JS,Anders R,et al.Functional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome[J].J Clin Invest,2002,110 (2):247-257.
[25] Kariya Y,Honma M,Hanamura A,et al.Rab27a and Rab27b Are Involved in Stimulation-Dependent RANKL Release From Secretory Lysosomes in Osteoblastic Cells[J].JBMR,2011,26 (4):689-703.
[26] Y.Kariya,M.Honma,H.Suzuki.RANKL secretion from secretory lysosomes in osteoblastic cells — The involvement of small GTPase Rab27a/b[J].Bone,2009,44(Supplement 1):S140.
[27] Nabavi N,Pustylnik S,Harrison RE.Rab GTPase Mediated Procollagen Trafficking in Ascorbic Acid Stimulated Osteoblasts[J].PLoS One,2012,7(9):e46265.
[28] Shimada-Sugawara M,Sakai E,Okamoto K,et al.Rab27A regulates transport of cell surface receptors modulating multinucleation and lysosome-related organelles in osteoclasts[J].Scientific Rep,2015(5):9620.
[29] Tang L,Yin Y,Liu J,et al.MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a[J].Cell Physiol Biochem,2017,43(4):1663-1672.
[30] Kronenberg HM.Developmental regulation of the growth plate[J].Nature,2003,423(6937):332-336.
[31] Yang L,Clinton JM,Blackburn ML,et al.Rab23 regulates differentiation of ATDC5 chondroprogenitor cells[J].J Biol Chem,2008,283(16):10649-10657.
[32] Wang Y,Ng EL,Tang BL.Rab23:what exactly does it traffic?[J].Traffic,2006,7(6):746-750.
[33] Evans TM,Ferguson C,Wainwright BJ,et al.Rab23,a negative regulator of hedgehog signaling,localizes to the plasma membrane and the endocytic pathway[J].Traffic,2003,4(12):869-884.
[34] Antebi B,Pelled G,Gazit D.Stem cell therapy for osteopo-rosis[J].Curr Osteoporosis Rep,2014,12(1):41-47.
[2] 鲁尚德.骨质疏松症病因病机研究概况[J].世界最新医学信息文摘,2016,16(38):44-45,51.
[3] Blanc L,Vidal M.New insights into the function of Rab GTPases in the context of exosomal secretion[J].Small GTPases.2018,9(1-2):95-106.
[4] 张岩.预防老年人骨质疏松[J].护士进修杂志,2010,25(3):195-197.
[5] Boivin G,Vedi S,Purdid DW,et al.Influence ofestrogen therapy Atconventional and high doses on the digree of mineralization of iliac bone tissue:a quantitativemicrora-diographic analysis in postmenopausalwomen[J].Bone,2005,36(3):562-567.
[6] 姚锦容,李彬强.1500例中老年妇女骨密度调查[J].社区医学杂志,2011,9(15):63-64.
[7] Bailey DA,McKay HA,Mirwald RL,et al.A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children:the university of Saskatchewan bone mineral accrual study[J].J Bone Miner Res.1999,14(10):1672-1679.
[8] Vuori IM.Dose-response of physical activity and low back pain,osteoarthritis,and osteoporosis[J].Med Sci Sports Exerc.2001,33(6 Suppl):S551-S586.
[9] 宋东伟,徐斌,王玉姝,等.选择性雌激素受体调节剂组织选择性作用研究进展[J].现代药物与临床,2014,29(2):206-210.
[10] Cervellati C,Bonaccorsi G,Cremonini E,et al.Oxidative stress and bone resorption interplay as a possible trigger for postmenopausal osteoporosis [J].Biomed Res Int,2014(2014):569563.
[11] 张晶,付勤.IL-17在绝经后骨质疏松方面的相关研究[J].中国骨质疏松杂志,2013,19(3):310-313.
[12] 杨剑.Rab3D蛋白促进肿瘤转移和Hsp90α质膜转运信号的研究[D].北京:清华大学,2015.
[13] Shimadal K,Uzawa K,Kato M,et al.Aberrant expression of RAB1A in human tongue cancer[J].Br J Cancer,2005,92(10):1915-1921.
[14] Croizet Berger K,Daumerie C,Couvreur M,et al.The endocytic catalysts,Rab5a and Rab7,are tandem regulators of thyroid hormone production[J].Proc Natl Acad Sci USA,2002,99(12):8277-8282.
[15] Calvo A,Xiao N,Kang J,et al.Alterations in gene expression profiles during prostate cancer progression:functional correlations to tumorigenicity and downregulation of selenoprotein-P in mouse and human tumors[J].Cancer Res,2002,62(18):5325-5335.
[16] Mor O,Nativ O,Stein A,et al.Molecular analysis of transitional cell carcinoma using c DNA microarray[J].Oncogene,2003,22(48):7702-7710.
[17] Wang W,Wyckoff JB,Frohlich VC,et al.Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling[J].Cancer Res,2002,62(21):6278-6288.
[18] Sorlie T,Tibshirani R,Parker J,et al.Repeated observation of breast tumor subtypes in independent gene expression data sets[J].Proc Natl Acad Sci USA,2003,100(14):8418-8123.
[19] Schaner ME,Ross DT,Ciaravino G,et al.Gene expression patterns in ovarian carcinomas[J].Mol Biol Cell,2003,14(11):4376-4386.
[20] Cha BH,Jung MJ,Moon BK,et al.Administration of taurour-sodeoxycholic acid enhances osteogenic differentiation of bone marrow derived mesenchymal stem cells and bone regeneration[J].Bone,2015(83):73-81.
[21] Li C,Wei G,Gu Q,et al.Donor Age and Cell Passage Affect Osteogenic Ability of Rat Bone Marrow Mesenchymal Stem Cells [J].Cell Biochemistry & Biophysics,2015,72(2):543-549.
[22] Itzstein C,Coxon FP,Rogers MJ.The regulation of osteoclast function and bone resorption by small GTPases[J].Small GTPases.2011,2(3):117-130.
[23] Pereira-Leal JB,Seabra MC.Evolution of the Rab family of small GTP-binding proteins[J].J Mol Biol,2001,313 (4):889-901.
[24] Barral DC,Ramalho JS,Anders R,et al.Functional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome[J].J Clin Invest,2002,110 (2):247-257.
[25] Kariya Y,Honma M,Hanamura A,et al.Rab27a and Rab27b Are Involved in Stimulation-Dependent RANKL Release From Secretory Lysosomes in Osteoblastic Cells[J].JBMR,2011,26 (4):689-703.
[26] Y.Kariya,M.Honma,H.Suzuki.RANKL secretion from secretory lysosomes in osteoblastic cells — The involvement of small GTPase Rab27a/b[J].Bone,2009,44(Supplement 1):S140.
[27] Nabavi N,Pustylnik S,Harrison RE.Rab GTPase Mediated Procollagen Trafficking in Ascorbic Acid Stimulated Osteoblasts[J].PLoS One,2012,7(9):e46265.
[28] Shimada-Sugawara M,Sakai E,Okamoto K,et al.Rab27A regulates transport of cell surface receptors modulating multinucleation and lysosome-related organelles in osteoclasts[J].Scientific Rep,2015(5):9620.
[29] Tang L,Yin Y,Liu J,et al.MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a[J].Cell Physiol Biochem,2017,43(4):1663-1672.
[30] Kronenberg HM.Developmental regulation of the growth plate[J].Nature,2003,423(6937):332-336.
[31] Yang L,Clinton JM,Blackburn ML,et al.Rab23 regulates differentiation of ATDC5 chondroprogenitor cells[J].J Biol Chem,2008,283(16):10649-10657.
[32] Wang Y,Ng EL,Tang BL.Rab23:what exactly does it traffic?[J].Traffic,2006,7(6):746-750.
[33] Evans TM,Ferguson C,Wainwright BJ,et al.Rab23,a negative regulator of hedgehog signaling,localizes to the plasma membrane and the endocytic pathway[J].Traffic,2003,4(12):869-884.
[34] Antebi B,Pelled G,Gazit D.Stem cell therapy for osteopo-rosis[J].Curr Osteoporosis Rep,2014,12(1):41-47.