骨组织工程研究中P75神经营养因子受体的作用及应用价值
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摘要
背景:P75神经营养因子受体属于低亲和力神经营养因子受体,它不仅在神经生长、发育和维持功能完整性等方面具有重要作用,而且与骨组织修复、增强干细胞特性等方面也密切相关。目的:对目前P75神经营养因子受体在骨组织修复及再生中的研究进展以及价值进行综述。方法:计算机检索中国生物医学文献数据库、CNKI数据库、PubMed数据库以及Elsevier数据库的相关文献,检索词为"骨修复,骨再生,P75,P75NTR,bone repair,bone regenerate,tooth development,facialnerve,stemcell"。查阅1987年9月至2018年4月期间收录的P75神经营养因子受体在骨组织再生修复方面的相关文章,最终纳入47篇文献进行结果分析。结果与结论:(1)研究报道P75神经营养因子受体能促进牙齿的发育和面神经的修复,促进骨组织的矿化和缩短骨愈合的时间,还能通过调节干细胞的特性来间接促进骨愈合;(2)也有研究者认为P75神经营养因子受体诱导的细胞凋亡可能会阻碍骨折的愈合,甚至导致骨折不愈合;(3)对于P75神经营养因子受体在骨组织修复方面所表现出双重作用的通路机制,未来还需要更深入的研究;(4)目前关于P75神经营养因子受体在骨组织修复的研究还仅仅局限于基础研究,临床应用的报道还很少。
BACKGROUND: P75 neurotrophin receptor holds low affinity, which not only plays an important role in nerve growth, development and maintenance of functional integrity, but also has a close relationship with bone tissue repair and stem cell enhancement. OBJECTIVE: To review the research progress and value of P75 neurotrophin receptor in bone tissue repair and regeneration. METHODS: A computer-based search of CBM, CNKI, PubMed and Elsevier was performed for retrieving articles concerning P75 neurotrophin receptor in bone tissue regeneration published from September 1987 to April 2018. The keywords were "P75, P75 NTR, bone repair, bone regenerate, tooth development, facial nerve, stem cell" in Chinese and English, respectively. Totally 47 eligible articles were included in final analysis. RESULTS AND CONCLUSION: P75 neurotrophin receptor has been reported to not only promote tooth development and facial nerve repair, but also promote mineralization of bone tissue and shorten bone healing time. It also indirectly promotes bone healing by regulating the characteristics of stem cells. However, some researchers believe that apoptosis induced by P75 neurotrophin receptor may hinder fracture healing and even lead to fracture failure. Whether P75 neurotrophin receptor can promote bone repair or inhibit bone tissue repair needs further investigation. At present, its research is still limited to basic research, and there are few reports on its clinical application.
BACKGROUND: P75 neurotrophin receptor holds low affinity, which not only plays an important role in nerve growth, development and maintenance of functional integrity, but also has a close relationship with bone tissue repair and stem cell enhancement. OBJECTIVE: To review the research progress and value of P75 neurotrophin receptor in bone tissue repair and regeneration. METHODS: A computer-based search of CBM, CNKI, PubMed and Elsevier was performed for retrieving articles concerning P75 neurotrophin receptor in bone tissue regeneration published from September 1987 to April 2018. The keywords were "P75, P75 NTR, bone repair, bone regenerate, tooth development, facial nerve, stem cell" in Chinese and English, respectively. Totally 47 eligible articles were included in final analysis. RESULTS AND CONCLUSION: P75 neurotrophin receptor has been reported to not only promote tooth development and facial nerve repair, but also promote mineralization of bone tissue and shorten bone healing time. It also indirectly promotes bone healing by regulating the characteristics of stem cells. However, some researchers believe that apoptosis induced by P75 neurotrophin receptor may hinder fracture healing and even lead to fracture failure. Whether P75 neurotrophin receptor can promote bone repair or inhibit bone tissue repair needs further investigation. At present, its research is still limited to basic research, and there are few reports on its clinical application.
引文
[1]Sun H, Zhe Q, Ying G, et al. In vitro and in vivo effects of rat kidney vascular endothelial cells on osteogenesis of rat bone marrow mesenchymal stem cells growing on polylactide-glycoli acid(PLGA)scaffolds. Biomed Eng Online.2007;6:41.
[2]韩倩,张志宏,刘红红,等.犬下颌骨骨缺损自我修复能力的电镜观察[J].安徽医药,2012,16(3):326-328.
[3]刘伟,赵光锋,喻任.转移生长因子-β1、碱性成纤维细胞生长因子、骨形态发生蛋白-2在大鼠骨质疏松骨折愈合骨痂中的表达[J].中华急诊医学杂志,2003,12(8):530-532.
[4]Levimontalcini R. The nerve growth factor 35 years later.Science. 1987;237(4819):1154-1162.
[5]魏传银,王丽梅,陈雪红,等.神经营养素受体p75^NTR介导的信号转导[J].细胞与分子免疫学杂志,2005,21(2):258-60.
[6]李家勇,王铭,彭称飞,et al.P75NTR在兔骨折不愈合局部组织中的表达及意义[J].中国骨质疏松杂志,2017,23(4):437-40.
[7]吴小莹,杨斌.脑源性神经营养因子与骨/牙组织发育代谢:促成或抑制细胞的增殖与分化?[J].中国组织工程研究. 2015,19(2):283-288.
[8]钟湘平,廖勇仕.TrkA、p75NTR在神经系统中的研究进展[J].社区医学杂志,2013,11(19):14-17.
[9]XL H, KC G. Structure of nerve growth factor complexed with the shared neurotrophin receptor p75. Science. 2004;304(5672):870-875.
[10]Vilar M, Charalampopoulos I, Kenchappa RS, et al. Activation of the p75 neurotrophin receptor through conformational rearrangement of disulphide-linked receptor dimers. Neuron.2009;62(1):72-83.
[11]Coulson EJ, May LM, Sykes AM, et al. The role of the p75neurotrophin receptor in cholinergic dysfunction in Alzheimer's disease. Neuroscientist. 2009;15(4):317-323.
[12]白氡,黄秉仁.神经营养因子低亲和力受体p75NTR信号通路的研究进展[J].中华危重病急救医学,2001,13(7):439-441.
[13]Tomellini E, Lagadec C, Polakowska R, et al. Role of p75neurotrophin receptor in stem cell biology:more than just a marker. Cell Mol Life Sci. 2014;71(13):2467-2481.
[14]Bl?chl A, Bl?chl R. A cell‐biological model of p75NTR signaling. J Neurochem. 2007, 102(2):289-305.
[15]Wen X, Liu L, Deng M, et al. Characterization of p75(+)ectomesenchymal stem cells from rat embryonic facial process tissue. Biochem Biophys Res Commun. 2012;427(1):5-10.
[16]Zhao M, Wen X, Li G, et al.[The capacity and biological characteristic of the p75 neurotrophin receptor-positive ectomesenchymal stem cell in vitro]. Zhonghua Kou Qiang Yi Xue Za Zhi. 2015;50(2):103-109.
[17]Rada T, Reis RL, Gomes ME. Distinct stem cells subpopulations isolated from human adipose tissue exhibit different chondrogenic and osteogenic differentiation potential.Stem Cell Rev. 2011;7(1):64-76.
[18]Ju YX, Wen XJ, Yang K, et al.[Expression of p75neurotrophin receptor during the mineralization of ectomesenchymal stem cells in vitro]. Zhonghua Kou Qiang Yi Xue Za Zhi. 2016;51(7):426-431.
[19]Yang K, Wang Y, Ju Y, et al. p75 neurotrophin receptor regulates differential mineralization of rat ectomesenchymal stem cells. Cell Proliferation. 2016; 50(1):e12290.
[20]Xing Y, Nie X, Chen G, et al. Comparison of P75 NTR-positive and-negative etcomesenchymal stem cell odontogenic differentiation through epithelial-mesenchymal interaction.Cell Prolif. 2016;49(2):185-194.
[21]Liu Q, Lei L, Yu T, et al. Effect of brain-derived neurotrophic factor on the neurogenesis and osteogenesis in bone engineering. Tissue Engineering Part A. 2018;10(5):462.
[22]Mikami Y, Ishii Y, Watanabe N, et al. CD271/p75(NTR)inhibits the differentiation of mesenchymal stem cells into osteogenic,adipogenic, chondrogenic, and myogenic lineages. Stem Cells Dev. 2011;20(5):901-913.
[23]Majdan M, Walsh G, Aloyz R, et al. TrkA mediates developmental sympathetic neuron survival in vivo by silencing an ongoing p75NTR-mediated death signal. Journal of Cell Biology. 2001;155(7):1275-1286.
[24]Akiyama Y, Mikami Y, Watanabe E, et al. The P75neurotrophin receptor regulates proliferation of the human MG63 osteoblast cell line. Differentiation. 2014; 87(3-4):111-118.
[25]Mikami Y, Suzuki S, Ishii Y, et al. The p75 neurotrophin receptor regulates MC3T3-E1 osteoblastic differentiation.Differentiation. 2012;84(5):392-399.
[26]Chartier SR, Mitchell SAT, Majuta LA, et al.Immunohistochemical localization of nerve growth factor,tropomyosin receptor kinase A, and p75 in the bone and articular cartilage of the mouse femur. Mol Pain. 2017;13:1744806917745465..
[27]王莹莹,储庆,杨琨,等. p75NTR敲除对小鼠股骨矿化发育的抑制作用[J].第三军医大学学报,2017,39(12):1245-1250.
[28]于立明,张伟,陈坤,等.神经生长因子及其受体在下颌骨骨折愈合中的表达及意义[J].实用口腔医学杂志,2011,27(4):460-464.
[29]张伟,于立明,吴亚东,等.神经生长因子受体(p75)在下颌骨骨折愈合中的表达及意义的研究[J].中国实验诊断学, 2006,23(7):255-257.
[30]Wang L, Zhou S, Liu B, et al. Locally applied nerve growth factor enhances bone consolidation in a rabbit model of mandibular distraction osteogenesis. J Orthop Res. 2006;24(12):2238-2245.
[31]王铭,彭称飞,段江涛,等.P75NTR介导细胞凋亡在骨折愈合过程中的研究进展[J].世界最新医学信息文摘,2018,18(6):81-83.
[32]Shen J, Chen X, Li H, et al. p75 neurotrophin receptor and its novel interaction partner, NIX, are involved in neuronal apoptosis after intracerebral hemorrhage. Cell Tissue Res.2017;368(1):13-27.
[33]Ahn BY, Saldanhagama RFG, Rahn JJ, et al. Glioma invasion mediated by the p75 neurotrophin receptor(p75NTR/CD271)requires regulated interaction with PDLIM1. Oncogene. 2016;35(11):1411-1422.
[34]Kang IK, Coimbra LS, Chen T, et al. Diabetes reduces mesenchymal stem cells in fracture healing through a TNFα-mediated mechanism. Diabetologia. 2015;58(3):633-642.
[35]Karnes JM, Daffner SD, Watkins CM. Multiple roles of tumor necrosis factor-alpha in fracture healing. Bone. 2015;78:87-93.
[36]刘凯,乔剑波,杨德文,等.骨折患者血清C-反应蛋白、纤维蛋白原表达变化及其意义[J].包头医学院学报, 2016,32(12):21-22.
[37]Barcelona PF, Sitaras N, Galan A, et al. p75NTR and Its Ligand ProNGF Activate Paracrine Mechanisms Etiological to the Vascular, Inflammatory, and Neurodegenerative Pathologies of Diabetic Retinopathy. J Neurosci. 2016;36(34):8826-8841.
[38]Schwabe P, Simon P, Kronbach Z, et al. A pilot study investigating the histology and growth factor content of human non-union tissue. Int Orthop. 2014;38(12):2623-2629.
[39]Koga T, Lee SY, Niikura T, et al. Effect of low-intensity pulsed ultrasound on bone morphogenetic protein 7-induced osteogenic differentiation of human nonunion tissue-derived cells in vitro. J Ultrasound Med. 2013;32(6):915-922.
[40]Sachs B, Passino M, Sikorski S, et al. ID:248 p75Neurotrophin Receptor Regulates Fibrinolysis via a cAMP/PKA Pathway. Journal of Thrombosis&Haemostasis.2006, 4(s1):142.
[41]Maes C, Kobayashi T, Selig MK, et al. Osteoblast Precursors,but Not Mature Osteoblasts, Move into Developing and Fractured Bones along with Invading Blood Vessels.Developmental Cell. 2010, 19(2):329-344.
[42]Caporali A, Meloni M, Nailor A, et al. p75NTR-dependent activation of NF-κB regulates microRNA-503 transcription and pericyte–endothelial crosstalk in diabetes after limb ischaemia.Nature Communications. 2015;6:8024.
[43]Shanab AY, Mysona BA, Matragoon S, et al. Silencing p75NTR prevents proNGF-induced endothelial cell death and development of acellular capillaries in rat retina. Mol Ther Methods Clin Dev. 2015;2:15013.
[44]Luukko K, Moshnyakov M, Sainio K, et al. Expression of neurotrophin receptors during rat tooth development is developmentally regulated, independent of innervation, and suggests functions in the regulation of morphogenesis and innervation. Dev Dyn. 1996; 206(1):87-99.
[45]Mitsiadis TA, Pagella P. Expression of Nerve Growth Factor(NGF), TrkA, and p75NTR in Developing Human Fetal Teeth.Front Physiol. 2016;7:338,
[46]张风河,魏奉才,杨丕山,等.对小鼠面神经损伤后脑内神经元再生的影响[J].口腔颌面外科杂志,2007,17(2):139-142.
[47]Oakley B, Witt M. Building sensory receptors on the tongue. J Neurocytol. 2004;33(6):631-646.
[2]韩倩,张志宏,刘红红,等.犬下颌骨骨缺损自我修复能力的电镜观察[J].安徽医药,2012,16(3):326-328.
[3]刘伟,赵光锋,喻任.转移生长因子-β1、碱性成纤维细胞生长因子、骨形态发生蛋白-2在大鼠骨质疏松骨折愈合骨痂中的表达[J].中华急诊医学杂志,2003,12(8):530-532.
[4]Levimontalcini R. The nerve growth factor 35 years later.Science. 1987;237(4819):1154-1162.
[5]魏传银,王丽梅,陈雪红,等.神经营养素受体p75^NTR介导的信号转导[J].细胞与分子免疫学杂志,2005,21(2):258-60.
[6]李家勇,王铭,彭称飞,et al.P75NTR在兔骨折不愈合局部组织中的表达及意义[J].中国骨质疏松杂志,2017,23(4):437-40.
[7]吴小莹,杨斌.脑源性神经营养因子与骨/牙组织发育代谢:促成或抑制细胞的增殖与分化?[J].中国组织工程研究. 2015,19(2):283-288.
[8]钟湘平,廖勇仕.TrkA、p75NTR在神经系统中的研究进展[J].社区医学杂志,2013,11(19):14-17.
[9]XL H, KC G. Structure of nerve growth factor complexed with the shared neurotrophin receptor p75. Science. 2004;304(5672):870-875.
[10]Vilar M, Charalampopoulos I, Kenchappa RS, et al. Activation of the p75 neurotrophin receptor through conformational rearrangement of disulphide-linked receptor dimers. Neuron.2009;62(1):72-83.
[11]Coulson EJ, May LM, Sykes AM, et al. The role of the p75neurotrophin receptor in cholinergic dysfunction in Alzheimer's disease. Neuroscientist. 2009;15(4):317-323.
[12]白氡,黄秉仁.神经营养因子低亲和力受体p75NTR信号通路的研究进展[J].中华危重病急救医学,2001,13(7):439-441.
[13]Tomellini E, Lagadec C, Polakowska R, et al. Role of p75neurotrophin receptor in stem cell biology:more than just a marker. Cell Mol Life Sci. 2014;71(13):2467-2481.
[14]Bl?chl A, Bl?chl R. A cell‐biological model of p75NTR signaling. J Neurochem. 2007, 102(2):289-305.
[15]Wen X, Liu L, Deng M, et al. Characterization of p75(+)ectomesenchymal stem cells from rat embryonic facial process tissue. Biochem Biophys Res Commun. 2012;427(1):5-10.
[16]Zhao M, Wen X, Li G, et al.[The capacity and biological characteristic of the p75 neurotrophin receptor-positive ectomesenchymal stem cell in vitro]. Zhonghua Kou Qiang Yi Xue Za Zhi. 2015;50(2):103-109.
[17]Rada T, Reis RL, Gomes ME. Distinct stem cells subpopulations isolated from human adipose tissue exhibit different chondrogenic and osteogenic differentiation potential.Stem Cell Rev. 2011;7(1):64-76.
[18]Ju YX, Wen XJ, Yang K, et al.[Expression of p75neurotrophin receptor during the mineralization of ectomesenchymal stem cells in vitro]. Zhonghua Kou Qiang Yi Xue Za Zhi. 2016;51(7):426-431.
[19]Yang K, Wang Y, Ju Y, et al. p75 neurotrophin receptor regulates differential mineralization of rat ectomesenchymal stem cells. Cell Proliferation. 2016; 50(1):e12290.
[20]Xing Y, Nie X, Chen G, et al. Comparison of P75 NTR-positive and-negative etcomesenchymal stem cell odontogenic differentiation through epithelial-mesenchymal interaction.Cell Prolif. 2016;49(2):185-194.
[21]Liu Q, Lei L, Yu T, et al. Effect of brain-derived neurotrophic factor on the neurogenesis and osteogenesis in bone engineering. Tissue Engineering Part A. 2018;10(5):462.
[22]Mikami Y, Ishii Y, Watanabe N, et al. CD271/p75(NTR)inhibits the differentiation of mesenchymal stem cells into osteogenic,adipogenic, chondrogenic, and myogenic lineages. Stem Cells Dev. 2011;20(5):901-913.
[23]Majdan M, Walsh G, Aloyz R, et al. TrkA mediates developmental sympathetic neuron survival in vivo by silencing an ongoing p75NTR-mediated death signal. Journal of Cell Biology. 2001;155(7):1275-1286.
[24]Akiyama Y, Mikami Y, Watanabe E, et al. The P75neurotrophin receptor regulates proliferation of the human MG63 osteoblast cell line. Differentiation. 2014; 87(3-4):111-118.
[25]Mikami Y, Suzuki S, Ishii Y, et al. The p75 neurotrophin receptor regulates MC3T3-E1 osteoblastic differentiation.Differentiation. 2012;84(5):392-399.
[26]Chartier SR, Mitchell SAT, Majuta LA, et al.Immunohistochemical localization of nerve growth factor,tropomyosin receptor kinase A, and p75 in the bone and articular cartilage of the mouse femur. Mol Pain. 2017;13:1744806917745465..
[27]王莹莹,储庆,杨琨,等. p75NTR敲除对小鼠股骨矿化发育的抑制作用[J].第三军医大学学报,2017,39(12):1245-1250.
[28]于立明,张伟,陈坤,等.神经生长因子及其受体在下颌骨骨折愈合中的表达及意义[J].实用口腔医学杂志,2011,27(4):460-464.
[29]张伟,于立明,吴亚东,等.神经生长因子受体(p75)在下颌骨骨折愈合中的表达及意义的研究[J].中国实验诊断学, 2006,23(7):255-257.
[30]Wang L, Zhou S, Liu B, et al. Locally applied nerve growth factor enhances bone consolidation in a rabbit model of mandibular distraction osteogenesis. J Orthop Res. 2006;24(12):2238-2245.
[31]王铭,彭称飞,段江涛,等.P75NTR介导细胞凋亡在骨折愈合过程中的研究进展[J].世界最新医学信息文摘,2018,18(6):81-83.
[32]Shen J, Chen X, Li H, et al. p75 neurotrophin receptor and its novel interaction partner, NIX, are involved in neuronal apoptosis after intracerebral hemorrhage. Cell Tissue Res.2017;368(1):13-27.
[33]Ahn BY, Saldanhagama RFG, Rahn JJ, et al. Glioma invasion mediated by the p75 neurotrophin receptor(p75NTR/CD271)requires regulated interaction with PDLIM1. Oncogene. 2016;35(11):1411-1422.
[34]Kang IK, Coimbra LS, Chen T, et al. Diabetes reduces mesenchymal stem cells in fracture healing through a TNFα-mediated mechanism. Diabetologia. 2015;58(3):633-642.
[35]Karnes JM, Daffner SD, Watkins CM. Multiple roles of tumor necrosis factor-alpha in fracture healing. Bone. 2015;78:87-93.
[36]刘凯,乔剑波,杨德文,等.骨折患者血清C-反应蛋白、纤维蛋白原表达变化及其意义[J].包头医学院学报, 2016,32(12):21-22.
[37]Barcelona PF, Sitaras N, Galan A, et al. p75NTR and Its Ligand ProNGF Activate Paracrine Mechanisms Etiological to the Vascular, Inflammatory, and Neurodegenerative Pathologies of Diabetic Retinopathy. J Neurosci. 2016;36(34):8826-8841.
[38]Schwabe P, Simon P, Kronbach Z, et al. A pilot study investigating the histology and growth factor content of human non-union tissue. Int Orthop. 2014;38(12):2623-2629.
[39]Koga T, Lee SY, Niikura T, et al. Effect of low-intensity pulsed ultrasound on bone morphogenetic protein 7-induced osteogenic differentiation of human nonunion tissue-derived cells in vitro. J Ultrasound Med. 2013;32(6):915-922.
[40]Sachs B, Passino M, Sikorski S, et al. ID:248 p75Neurotrophin Receptor Regulates Fibrinolysis via a cAMP/PKA Pathway. Journal of Thrombosis&Haemostasis.2006, 4(s1):142.
[41]Maes C, Kobayashi T, Selig MK, et al. Osteoblast Precursors,but Not Mature Osteoblasts, Move into Developing and Fractured Bones along with Invading Blood Vessels.Developmental Cell. 2010, 19(2):329-344.
[42]Caporali A, Meloni M, Nailor A, et al. p75NTR-dependent activation of NF-κB regulates microRNA-503 transcription and pericyte–endothelial crosstalk in diabetes after limb ischaemia.Nature Communications. 2015;6:8024.
[43]Shanab AY, Mysona BA, Matragoon S, et al. Silencing p75NTR prevents proNGF-induced endothelial cell death and development of acellular capillaries in rat retina. Mol Ther Methods Clin Dev. 2015;2:15013.
[44]Luukko K, Moshnyakov M, Sainio K, et al. Expression of neurotrophin receptors during rat tooth development is developmentally regulated, independent of innervation, and suggests functions in the regulation of morphogenesis and innervation. Dev Dyn. 1996; 206(1):87-99.
[45]Mitsiadis TA, Pagella P. Expression of Nerve Growth Factor(NGF), TrkA, and p75NTR in Developing Human Fetal Teeth.Front Physiol. 2016;7:338,
[46]张风河,魏奉才,杨丕山,等.对小鼠面神经损伤后脑内神经元再生的影响[J].口腔颌面外科杂志,2007,17(2):139-142.
[47]Oakley B, Witt M. Building sensory receptors on the tongue. J Neurocytol. 2004;33(6):631-646.