促丝裂原激活蛋白激酶在牙髓干细胞向成牙本质细胞分化和牙髓损伤修复中的作用
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摘要
通过诱导牙髓干细胞(DPSC)向成牙本质细胞方向分化,龋源性牙髓炎的治疗将不再局限于根管治疗这一临床选择,修复治疗也不再成为缺失牙治疗的唯一方案。促丝裂原激活蛋白激酶(MAPK),尤其是P38MAPK通过直接或间接磷酸化特定的转录因子,将细胞外刺激信号转导至细胞及其核内,从而引起一系列细胞生物学反应,如细胞增殖、分化、转化和程序性死亡。骨形态发生蛋白-2、矿物三氧化物聚合体和Biodentine皆可诱导DPSC向成牙本质细胞分化,而三者正是通过MAPK信号转导通路发挥作用的。在组织工程支架诱导DPSC分化过程中,支架材料通过激活P38MAPK信号转导通路促进了DPSC的分化。此外,MAPK信号转导通路参与牙髓损伤修复中DPSC的迁移、黏附和分化,参与牙髓损伤修复中牙本质的形成。由于MAPK信号转导通路在细胞增殖、分化和生存等过程中都起着十分关键的作用,因此,深入研究其反应分子、作用底物和作用机制有着重要的理论和临床意义。
Several more alternatives can be offered for the treatment of carious pulp disease and restoration of lost teeth by inducing the odontoblast differentiation of dental pulp stem cell(DPSC). Mitogen-activated protein kinases(MAPK), specifically P38 MAPK, are involved in various cellular functions, such as cell proliferation, differentiation, and apoptosis, by transducing extracellular signal to the cell and nucleus through transcription factor phosphorylation. In addition, bone morphogenetic protein-2, mineral trioxide aggregate, and biodentin can induce the odontoblast differentiation of DPSC by regulating MAPK signaling pathway and certain scaffolds in tissue engineering. Moreover, the MAPK signaling pathway performs an important function in the migration, adhesion, and differentiation of DPSC during dental pulp injury. Based on the key function of MAPK signaling pathway, further study on the molecule, substrate, and mechanisms is crucial.
Several more alternatives can be offered for the treatment of carious pulp disease and restoration of lost teeth by inducing the odontoblast differentiation of dental pulp stem cell(DPSC). Mitogen-activated protein kinases(MAPK), specifically P38 MAPK, are involved in various cellular functions, such as cell proliferation, differentiation, and apoptosis, by transducing extracellular signal to the cell and nucleus through transcription factor phosphorylation. In addition, bone morphogenetic protein-2, mineral trioxide aggregate, and biodentin can induce the odontoblast differentiation of DPSC by regulating MAPK signaling pathway and certain scaffolds in tissue engineering. Moreover, the MAPK signaling pathway performs an important function in the migration, adhesion, and differentiation of DPSC during dental pulp injury. Based on the key function of MAPK signaling pathway, further study on the molecule, substrate, and mechanisms is crucial.
引文
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[28]Bikkavilli RK,Feigin ME,Malbon CC.p38 mitogenactivated protein kinase regulates canonical Wntbeta-catenin signaling by inactivation of GSK3beta[J].J Cell Sci,2008,121(Pt 21):3598-3607.
[29]Faust D,Schmitt C,Oesch F,et al.Differential p38-dependent signalling in response to cellular stress and mitogenic stimulation in f ibroblasts[J].Cell Commun Signal,2012,10:6.
[30]Wood CD,Thornton TM,Sabio G,et al.Nuclear localization of P38MAPK in response to DNA damage[J].Int J Biol Sci,2009,5(5):428-437.
[31]Gong X,Ming X,Deng P,et al.Mechanisms regulating the nuclear translocation of p38 MAP kinase[J].J Cell Biochem,2010,110(6):1420-1429.
[32]Ruch JV.Odontoblast commitment and differentiation[J].Biochem Cell Biol,1998,76(6):923-938.
[2]Gronthos S,Brahim J,Li W,et al.Stem cell properties of human dental pulp stem cells[J].J Dent Res2002,81(8):531-535.
[3]Huang AH,Chen YK,Lin LM,et al.Isolation and characterization of dental pulp stem cells from a supernumerary tooth[J].J Oral Pathol Med,2008,37(9):571-574.
[4]Harada H,Kettunen P,Jung HS,et al.Localization of putative stem cells in dental epithelium and their association with Notch and FGF signaling[J].J Cell Biol,1999,147(1):105-120.
[5]Téclès O,Laurent P,Zygouritsas S,et al.Activation of human dental pulp progenitor/stem cells in response to odontoblast injury[J].Arch Oral Biol,2005,50(2):103-108.
[6]Shi S,Robey PG,Gronthos S.Comparison of human dental pulp and bone marrow stromal stem cells by c DNA microarray analysis[J].Bone,2001,29(6):532-539.
[7]Blüthgen N,Legewie S.Systems analysis of MAPKsignal transduction[J].Essays Biochem,2008,45:95-107.
[8]Patil CS,Kirkwood KL.P38MAPK signaling in oralrelated diseases[J].J Dent Res,2007,86(9):812-825.
[9]Ruch JV,Lesot H,Bègue-Kirn C.Odontoblast differentiation[J].Int J Dev Biol,1995,39(1):51-68.
[10]Smith AJ,Cassidy N,Perry H,et al.Reactionary dentinogenesis[J].Int J Dev Biol,1995,39(1):273-280.
[11]Qin W,Lin ZM,Deng R,et al.P38a MAPK is involved in BMP-2-induced odontoblastic differentiation of human dental pulp cells[J].Int Endod J2012,45(3):224-233.
[12]Zhao X,He W,Song Z,et al.Mineral trioxide aggregate promotes odontoblastic differentiation via mitogen-activated protein kinase pathway in human dental pulp stem cells[J].Mol Biol Rep,2012,39(1):215-220.
[13]Luo Z,Kohli MR,Yu Q,et al.Biodentine induces human dental pulp stem cell differentiation through mitogen-activated protein kinase and calcium-/calmodulin-dependent protein kinaseⅡpathways[J].J Endod,2014,40(7):937-942.
[14]Simon SR,Berdal A,Cooper PR,et al.Dentin-pulp complex regeneration:from lab to clinic[J].Adv Dent Res,2011,23(3):340-345.
[15]Zhang H,Liu S,Zhou Y,et al.Natural mineralized scaffolds promote the dentinogenic potential of dental pulp stem cells via the mitogen-activated protein kinase signaling pathway[J].Tissue Eng Part A,2012,18(7/8):677-691.
[16]Goldberg M,Smith AJ.Cells and extracellular matrices of dentin and pulp:a biological basis for repair and tissue engenerring[J].Crit Rev Oral Biol Med,2004,15(1):13-27.
[17]Fitzgerald M,Chiego DJ,Heys DR.Autoradiographic analysis of odontoblast replacement following pulp exposure in primate teeth[J].Arch Oral Biol,1990,35(9):707-715.
[18]Sloan AJ,Smith AJ.Stem cells and the dental pulp:potential roles in dentine regeneration and repair[J].Oral Dis,2007,13(2):151-157.
[19]Hosoya S,Matsushima K,Ohbayashi E,et al.Stimulation of interleukin-1beta-independent interleukin-6production in human dental pulp cells by lipopolysaccharide[J].Biochem Mol Med,1996,59(2):138-143.
[20]Warfvinge J.Morphometric analysis of teeth with infl amed pulp[J].J Dent Res,1987,66(1):78-83.
[21]Li D,Fu L,Zhang Y,et al.The effects of LPS on adhesion and migration of human dental pulp stem cells in vitro[J].J Dent,2014,42(10):1327-1334.
[22]He W,Wang Z,Luo Z,et al.LPS promote the odontoblastic differentiation of human dental pulp stem cells via MAPK signaling pathway[J].J Cell Physiol,2015,230(3):554-561.
[23]Simon S,Smith AJ,Berdal A,et al.The MAP kinase pathway is involved in odontoblast stimulation via p38 phosphorylation[J].J Endod,2010,36(2):256-259.
[24]Güven G,Altun C,Günhan O,et al.Co-expression of cyclooxygenase-2 and vascular endothelial growth factor in inflamed human pulp:an immunohistochemical study[J].J Endod,2007,33(1):18-20.
[25]Yoshida S.A scanning electron microscope study of vascular development in the dental papilla of prenatal rat molars[J].Anat Embryol,1991,183(4):379-384.
[26]Botero TM,Son JS,Vodopyanov D,et al.MAPKsignaling is required for LPS-induced VEGF in pulp stem cells[J].J Dent Res,2010,89(3):264-269.
[27]Vandomme J,Touil Y,Ostyn P,et al.Insulin-like growth factor 1 receptor and p38 mitogen-activated protein kinase signals inversely regulate signal transducer and activator of transcription 3 activity to control human dental pulp stem cell quiescence propagation,and differentiation[J].Stem Cells Dev2014,23(8):839-851.
[28]Bikkavilli RK,Feigin ME,Malbon CC.p38 mitogenactivated protein kinase regulates canonical Wntbeta-catenin signaling by inactivation of GSK3beta[J].J Cell Sci,2008,121(Pt 21):3598-3607.
[29]Faust D,Schmitt C,Oesch F,et al.Differential p38-dependent signalling in response to cellular stress and mitogenic stimulation in f ibroblasts[J].Cell Commun Signal,2012,10:6.
[30]Wood CD,Thornton TM,Sabio G,et al.Nuclear localization of P38MAPK in response to DNA damage[J].Int J Biol Sci,2009,5(5):428-437.
[31]Gong X,Ming X,Deng P,et al.Mechanisms regulating the nuclear translocation of p38 MAP kinase[J].J Cell Biochem,2010,110(6):1420-1429.
[32]Ruch JV.Odontoblast commitment and differentiation[J].Biochem Cell Biol,1998,76(6):923-938.