摘要
乳牙根是人体中唯一能够进行生理性吸收的硬组织,其正常吸收是恒牙萌出的关键。破骨细胞(OC)和破牙细胞(OD)在此过程中发挥了重要的调控作用,现已明确有多种调控因子参与了破骨细胞和破牙细胞的增殖、分化、激活等骨吸收过程。
CK为番木瓜家族中的半胱氨酸蛋白酶成员,具有蛋白水解酶的特性,能够水解Ⅰ型胶原等骨基质蛋白,对破骨细胞、破牙细胞的形成和骨吸收有重要作用。FGFR1为成纤维细胞因子受体,能够与相应配体结合,调控成骨细胞及破骨细胞的增殖分化及骨形成。
本研究利用HE染色观察犬乳恒牙替换过程中组织形态的变化,TRAP染色观察破骨细胞、破牙细胞及其前体细胞的分布及数量变化,免疫组化方法检测犬乳恒牙替换过程中CK及FGFR1的表达。
结果表明:乳牙根吸收呈间断性,分静止期和活跃期,乳牙根吸收起始阶段组织形态稳定,晚期牙根及牙槽骨吸收活跃,同时骨改建明显。吸收活跃期破骨/破牙细胞及其前体细胞分布广泛,数量明显多于乳牙根稳定组、吸收早期组及恒牙列初期。
吸收活跃期破骨/破牙细胞内CK免疫组化强阳性,染色强度明显高于乳牙根稳定组、吸收早期组及恒牙列初期。恒牙胚发育过程中成釉细胞、成牙本质细胞及周围牙囊组织CK免疫组化染色阳性。表明CK作用于破骨细胞、破牙细胞、成釉细胞、成牙本质细胞及周围牙囊组织参与乳牙根的生理性吸收、恒牙萌出。
吸收活跃期破骨/破牙细胞、成骨细胞内FGFR1免疫组化强阳性,染色强度明显高于乳牙根稳定组、吸收早期组及恒牙列初期。恒牙胚发育过程中成釉细胞、成牙本质细胞及周围牙囊组织FGFR1免疫组化染色阳性。提示FGFR1作用破骨细胞、破牙细胞、成骨细胞、成釉细胞、成牙本质细胞及周围牙囊组织参与乳牙根的生理性吸收及恒牙的萌出。FGFR1一方面直接对破骨细胞及破牙细胞产生调控作用,另一方面通过成骨细胞间接对破骨细胞及破牙细胞产生调控作用。
The root of primary teeth is the hard tissue which can be resorbed under normalcircumstances only, regular absorption is the key to the permanent teeth eruption. Osteoclasts(OC) and odentoclast(OD) play important role in this process,and many factors have beenconfirmed to involve proliferation differentiation、activation of OC/OD.
CK is a novel member of the papain family of cysteine, which has an character ofproteolytic enzyme,can hydrolyze Collagen typeⅠof bone matrix proteins,and play a majorrole in formation of OC/OD and bone resorption. FGFR1is the receptor of FGF,which cancombine with the relevant ligand,and regulate and control the osteoblast (OB)and OC andbone formation.
In this research the changes of morphology were watched in the process of replacementof the primary and permanent teeth of the local dog through HE.the changes of the numberof OC/OD and its precursor cells were observe by TRAP.The expression of CK andFGFR1were detected by immunohistochemistry(IHC). The Result Show that the absorptionof primary tooth root is interrupted,contains resting stage and active phase, histomor-phological features was stable at the start, later primary tooth root and alveolar boneabsorption become active and bone remodeling shows lively. the number and distribution ofOC/OD and its precursor cells in active phase of absorption is larger and more extensivethan other groups.
CK in OC/OD in active phase of absorption show strong positive signals though IHCstains. positive signals is obviously stronger than the stable primary teeth group, earlyresorption of primary tooth group and early permanent teeth. In the process of developmentof permanent teeth, CK in ameloblast、odontoblast、dental follicle display strong positivesignals though IHC stains. Those imply that Ck take part in the primary teeth physiologicalabsorption and permanent teeth eruption though affecting OC/OD、ameloblast、odontoblast、dental follicle.
FGFR1in OC/OD、OB in active phase of absorption show strong positive signalsthough IHC stains. positive signals is obviously stronger than the stable primary teeth group,early resorption of primary tooth group and early permanent teeth. in the process of development of permanent teeth, FGFR1in ameloblast、odontoblast、dental follicle displaystrong positive signals though IHC stains. Those imply that FGFR1take part in the primaryteeth physiological absorption and permanent teeth eruption though affecting OC/OD、ameloblast、odontoblast、dental follicle. FGFR1regulate and control OC/OD directly andthough OB indirectly.
引文
[1]杨富生,方军,蔡伟英等.2839名儿童乳牙滞留状况分析[J].牙体牙髓牙周病学,2000,10(1):37-38.
[2] Sahara N. Cellular Events at the Onset of Physiological Root Resorption in RabbitDeciduous Teeth.[J] Anat Rec.,2001,264(4):387-396.
[3] Holding CA, Findlay DM, Stamenkov R etal. The correlation of RANK, RANKL andTNFalpha expression with bone loss volume and polyethylene wear debris around hipimplants.[J] Biomaterials.2006,27(30):5212-5219.
[4] Hemingway F, Taylor R, Knowles HJ etal.RANKL-independent human osteoclastformation with APRIL, BAFF, NGF, IGF I and IGF II.[J]Bone.2011,48(4):938-944.
[5]曲勃颖,黄洋,赵晶等.犬乳恒牙替换期间活化T细胞核因子NFATc1表达的研究.[J]现代口腔医学杂志,2009,23(6):627-630.
[6]赵晴潇,贾艳萍.前组织蛋白酶原K调节骨吸收的研究进展[J].中国兽医杂志2009,45(9):49-50.
[7] Kiviranta R, Morko J, Alatalo SL. Impaired bone resorption in cathepsin K-deficientmice is partially compensated for by enhanced osteoclastogenesis and increasedexpression of other proteases via an increased RANKL/OPG ratio.[J] Bone.2005,36(1):159-172.
[8] Yasuo Tsuji,Takayoshi Yamaza, Mizuho A, et al.Expression of cathepsin K mRNA andprotein in odontoclasts after experimental tooth movement in the mouse maxilla by insitu hybridization and immunoelectron microscopy[J].Cell Tissue Res,2001,303(3):359–369.
[9] Chikazu D, Hakeda Y, Ogata N, etal.Fibroblast growth factor (FGF)-2directly stimulatesmature osteoclast function through activation of FGF receptor1and p42/p44MAPkinase[J].J Biol Chem.2000,275(40):31444-31450.
[10] Lu X, Su N, Yang J, etal,Fibroblast growth factor receptor1regulates the differentiationand activation of osteoclasts through Erk1/2pathway[J]. Biochem Biophys ResCommun,2009,390(3):494-499.
[11] Bufalino A, Paranaíba LM, Gouvêa AF.Cleidocranial dysplasia: oral features andgenetic analysis of11patients.[J]Oral Dis.2012,18(2):184-190.
[12]杨祥,张趁英,郑树国.颅骨锁骨发育不良患者乳牙牙根吸收特点及牙齿结构分析.[J]北京大学学报2011,43(1):98-101.
[13] Caracas HP, Figueiredo PS, Mestrinho HD etal.Pycnodysostosis with craniosynostosis:case report of the craniofacial and oral features.[J]Clin Dysmorphol.2012,21(1):19-21.
[14] Feldman GJ, Robin NH, Brueton LA, etal.A gene for cleidocranial dysplasia maps tothe short arm of chromosome6[J]. Am J Hum Genet.1995,56(4):938-943.
[15] Kong MS, Harford R, O'Neill JT etal.Keratosis punctata palmoplantaris controlled withtopical retinoids: a case report and review of the literature[J]. Cutis,2004,74(3):173-179.
[16] Salamon T, Stoli V, Lazovi-Tepavac O, etal.Peculiar findings in a family withkeratodermia palmo-plantaris papulosa Buschke-Fischer-Brauer[J]. Hum Genet.1982,60(4):314-9.
[17] George A, Evans CA.Detection of root resorption using dentin and bone markers. Ort-hod Craniofac Res.[J].2009,12(3):229-235.
[18] Sasaki T, Watanabe C, Shimizu Possible role of cementoblasts in the resorbant organ ofhuman deciduous teeth during root resorption [J].J Periodontal Res,1990,25(3):143-151.
[19]刘正,边专.口腔生物学[M].北京:人民卫生出版社,2007.
[20] Wittrant Y, Theoleyre S, Coullaud S, etal.Relevance of an in vitro osteoclastogenesissystem tostudy receptor activator of NF-_B ligand and osteoprotegerin biologicalactivities [J]. Exp Cell Res,2004,293(2):292-301.
[21] Troen BR. Molecular mechanisms underlying osteoclast formation and activation[J].Exp Gerontol,2003,38(6):605-614.
[22] Trofimov S, Pantsulaia I, Kodoylinsky E, Livshits G. Circulating levels of receptoractivator of nuclear factor-_B ligand/osteoprotegerin/macrophage-colony stimulatingfactor in a presumablyheathy human population[J].Eur J Endocrinol2004,150(3):305-311.
[23] Liu D, Xu JK, Figliomeni L,et al. Expression of RANKL and OPG mRNA in periodo-ntaldisease: possible involvement in bone destruction[J].Int J MolMed,2003,11(1):17-21.
[24] Crotti T, Smith MD, Hirsch R,et al. Receptor activator of NF_B ligand (RANKL) andosteoprotegerin (OPG) protein expression in periodontitis[J]. J Periodont Res,2003,38(4):380-387.
[25] Sahara N. Cellular Events at the Onset of Physiological Root Resorption in RabbitDeciduous Teeth [J]. Anat Rec.,2001,264(4):387-396.
[26] Holding CA, Findlay DM, Stamenkov RThe correlation of RANK, RANKL andTNFalpha expression with bone loss volume and polyethylene wear debris around hipimplants[J].Biomaterials,2006,27(30):5212-5219.
[27] Hemingway F, Taylor R, Knowles HJ etal.RANKL-independent human osteoclast form-ation with APRIL, BAFF, NGF, IGF I and IGF II [J].Bone.,2011,48(4):938-944.
[28] McManus S, Chamoux E, Bisson M, Roux S. Modulation of tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL) receptors in a human osteoclast model invitro.[J]Format Apoptosis.2012,17(2):121-131.
[29] Jontell M, Okiji T, Dahlgren U, Bergenholtz G. Immune defense mechanisms of thedental pulp.[J]. Crit Rev Oral Biol Med.1998,9(2):179-200.
[30] Sakurai K, Okiji T, Suda H.Co-increase of nerve fibers and HLA-DR-and/or factor-XIIIa-expressing dendritic cells in dentinal caries-affected regions of the human dentalpulp: an immunohistochemical study.[J]J Dent Res,1999,78(10):1596-608
[31] Goldberg M, Farges JC, Lacerda-Pinheiro S, etal.Inflammatory and immunologicalaspects of dental pulp repair[J].Pharmacol Res.2008,58(2):137-147.
[32] Angelova A, Takagi Y, Okiji T, Kaneko T, Yamashita Y.Immunocompetent cells in thepulp of human deciduous teeth.[J] Arch Oral Biol.2004,49(1):29-36.
[33] Sim ek S, Durutürk L.A flow cytometric analysis of the biodefensive response of decid-uous tooth pulp to carious stimuli during physiological root resorption.[J]Arch OralBiol.2005,50(5):461-468.
[34] Horwood NJ, Kartsogiannis V, Quinn JM etal.Activated T lymphocytes support osteo-clast formation in vitro [J]. Biochem Biophys Res Commun.1999,265(1):144-150.
[35] Eronat C, Eronat N, Aktug M.Histological investigation of physiologically resorbingprimary teeth using Ag-NOR staining method [J]. Int J Paediatr Dent.2002,12(3):207-14.
[36] Sahara N, Okafuji N, Toyoki A.Odontoclastic resorption at the pulpal surface of coronaldentin prior to the shedding of human deciduous teeth [J] Arch Histol Cytol,1992,5(3):273-285.
[37] Yildirim S, Yapar M, Sermet U,etal.The role of dental pulp cells in resorption of decidu-ous teeth.[J] Oral Surg Oral Med Oral Pathol Oral Radiol Endod.2008,105(1):113-120.
[38] Park SH, Hsiao GY, Huang GT.Role of substance P and calcitonin gene-related peptidein the regulation of interleukin-8and monocyte chemotactic protein-1expression inhuman dental pulp[J]. Int Endod J,2004,7(3):185-192.
[39] Lossd rfer S, G tz W, J ger A.Immunohistochemical localization of receptor activatorof nuclear factor kappaB (RANK) and its ligand (RANKL) in human deciduous teeth.[J]Calcif Tissue Int.2002,71(1):45-52.
[40] MacNeil RL, D'Errico JA, Ouyang H, Isolation of murine cementoblasts: unique cellsor uniquely-positioned osteoblasts?[J] Eur J Oral Sci.1998,106(1):350-356.
[41] Tenorio D, Cruchley A, Hughes FJ.Immunocytochemical investigation of the ratcem-entoblast phenotype.[J] J Periodontal Res.1993,28(6):411-419.
[42] Shimizu N, Yamaguchi M, Goseki T etal.Cyclic-tension force stimulates interleukin-1beta production by human periodontal ligament cells.[J] J Periodontal Res.1994,29(5):328-233.
[43] Shimizu N, Yamaguchi M, Uesu K, etal.Stimulation of prostaglandin E2and inter-leukin1beta production from old rat periodontal ligament cells subjected to mechanicalstress.[J]J Gerontol A Biol Sci Med Sci.2000,55(10):489-495.
[44] Takahashi N, Akatsu T, Udagawa N, etal.Osteoblastic cells are involved in osteoclastformation.[J] Endocrinology.1988,123(5):2600-2602.
[45] Kanzaki H, Chiba M, Shimizu Y, etal.Dual regulation of osteoclast differentiation byperiodontal ligament cells through RANKL stimulation and OPG inhibition.[J] J DentRes.2001,80(3):887-891.
[46] Hasegawa T, Yoshimura Y, Kikuiri T Expression of receptor activator of NF-kappa Bligand and osteoprotegerin in culture of human periodontal ligament cells.[J] JPeriodontal Res.2002,37(6):405-411.
[47] Shiraishi C, Hara Y, Abe Y,etal.stopathological study of the role of periodontal ligamenttissue in root resorption in the rat [J]. Arch Oral Biol,2001,46(2):99-107.
[48] Bille ML, Thomsen B, Kjaer Apoptosis in the human periodontal membrane evaluatedin primary and permanent teeth[J].Acta Odontol Scand.2011,69(6):385-388.
[49] Fukushima H, Kajiya H, Takada K, etal.Expression and role of RANKL in periodontalligament cells during physiological root-resorption in human deciduous teeth[J]. Eur JOral Sci.2003,111(4):346-352.
[50] Tetsuya Goto, Takayoshi Yamaza etal.Cathepsins in the osteoclast[J].J Electron Mic-rosc (Tokyo),2003,52(6):551–558.
[51] Lecaille F, Bro¨mme D, LalmanachG.Biochemical properties and regulation of cath-epsin K[J].Biochimie,2008,90(2):208-226.
[52] Yang J, Shang GD, zhang YQ, et al. study of a novel antiosteoporosis screening modeltrgeted on cathepsin k[J]. Biomed Environ Sci,2004,17(3):273-280.
[53]吴艳.综述组织蛋白酶K与骨质疏松的研究进展[J].中国骨质疏松杂志2006,12(5):522-524.
[54] Walker DG.Bone resorption restored in osteopetrotic mice by transplants of normal bonemarrow and spleen cells.[J]Science.1975,190(4216):784-785.
[55] Ross FP, Chappel J, Alvarez JI, etal. Interactions between the bone matrix proteinsosteopontin and bone sialoprotein and the osteoclast integrin alpha v beta3potentiatebone resorption. J Biol Chem.[J]1993,268(13):9901-7.
[56] Roux S, Pichaud F, Quinn J,etal.Effects of prostaglandins on human hematopoieticosteoclast precursors.[J] Endocrinology.1997,138(4):1476-82.
[57] Brucer, Troen. The Regulation of Cathepsin K Gene Expression[J].Ann N Y AcadSci,2006,4(1068):165–172.
[58] Troen B.R. c-Jun Suppresses and JunB Enhances the stimulation of Cathepsin K pro-moter activity by NFAT2in RAW264.7cells[J]. Bone Miner.Res,2005,(20):372-375
[59] Mansky KC,Sankar U,Han J,et al. Microphthalmia transcriptionfactor is a target of thep38MAPK pathway in response toreceptor activator of NF-kB ligand signaling[J].JBiol Chem,2002,277(13):11077-11083.
[60] Matrixetall, Jean-marie delaisse,thomasl et al.proteinases(MMP) and Cathepsin Kcontribute differently to steoclastic activities[J].Microsc Res Tech,2003,61(6):504–513
[61] Montonen M, Li TF, Lukinmaa PL, et al. RANKL and Cathepsin K in diffusesclerosing osteomyelitis of the mandible[J]. Oral Pathol Med,2006,35(10):620–625.
[62] MakioM, Otogoto J. Exp ression of cathep sin-K in gingival crevicular fluid ofpatients with periodontitis[J]. Arch Oral Biol,2007,52(9):894-898.
[63] Wittrant Y, Theoleyre S, Coullaud S, etal. Relevance of an in vitro osteoclastogenesissystem tostudy receptor activator of NF-_B ligand and osteoprotegerin biologicalactivities[J]. Exp Cell Res2004,293(2):292-301.
[64] Knights V, Cook SJ.De-regulated FGF receptors as therapeutic targets in cancer.[J]Pharmacol Ther.2010,125(1):105-117.
[65] Olsen SK, Garbi M, Zampieri N, Fibroblast growth factor (FGF) homologous factorsshare structural but not functional homology with FGFs [J]. J Biol Chem.2003,278(36):34226-34223.
[66] Plotnikov AN, Schlessinger J, Hubbard SRetal.Structural basis for FGF receptordimerization and activation.[J] Cell.1999,98(5):641-650.
[67] Beenken A, Mohammadi M.etal.The FGF family: biology, pathophysiology and therapy.Nat Rev Drug Discov[J].2009,8(3):235-253.
[68] Sleeman M, Fraser J, McDonald M,etal.Identification of a new fibroblast growth factorreceptor, FGFR5.[J]Gene.2001,271(2):171-182.
[69] Olsen SK, Ibrahimi OA, Raucci A, Insights into the molecular basis for fibroblastgrowth factor receptor autoinhibition and ligand-binding promiscuity.[J] Proc NatlAcad Sci U S A.2004,101(4):935-940.
[70] Bertrand S, Somorjai I, Garcia-Fernandez J.FGFRL1is a neglected putative actor of theFGF signalling pathway present in all major metazoan phyla [J].BMC Evol Biol.2009,9(2)226-230.
[71]Hamidouche Z, Fromigué O etal.Autocrine fibroblast growth factor18mediatesdexamethasone-induced osteogenic differentiation of murine mesenchymal stem cells.[J]J Cell Physiol.2010,24(2):509-515.
[72] Yan D, Chen D, Cool SM,etal.Fibroblast growth factor receptor1is principally respo-nsible for fibroblast growth factor2-induced catabolic activities in human articularchondrocytes. Arthritis Res Ther.[J]2011,13(4):130.
[73] Park J, Park OJ, Yoon WJ, etal.Functional characterization of a novel FGFR2mutation,E731K, in craniosynostosis[J]. J Cell Biochem.2012,113(2):457,464.
[74] Kaabeche K, Lemonnier J, Le Mée S,Cbl-mediated degradation of Lyn and Fyn inducedby constitutive fibroblast growth factor receptor-2activation supports osteoblastdifferentiation[J]. J Biol Chem.2004,279(35):36259-36267.
[75] Degnin CR, Laederich MB, Horton WA etal.Ligand activation leads to regulatedintramembrane proteolysis of fibroblast growth factor receptor3[J]. Mol Biol Cell.2011,22(20):3861-3873.
[76]秦晗,杨富生,吴礼安等.降钙素对人骨巨细胞瘤组织中破骨细胞的影响.[J]现代口腔医学杂志,2008,22(3):283-285.
[77] Nakagawa N, Yasuda H, Yano K etal.Basic fibroblast growth factor induces osteoclastformation by reciprocally regulating the production of osteoclast differentiation factorand osteoclastogenesis inhibitory factor in mouse osteoblastic cells[J]. BiochemBiophys Res Commun.1999,265(1):158-163.
[78] Weizmann S, Tong A, Reich A,FGF upregulates osteopontin in epiphyseal growth platechondrocytes: implications for endochondral ossification[J].. Matrix Biol.2005,24(8):520-529.
[79]Liu Z, Lavine KJ, Hung IH etal.FGF18is required for early chondrocyte proliferation,hypertrophy and vascular invasion of the growth plate[J].. Dev Biol.2007,302(1):80-91.
[80] Chikazu D, Hakeda Y, Ogata N, etal.Fibroblast growth factor (FGF)-2directly stimul-ates mature osteoclast function through activation of FGF receptor1and p42/p44MAPkinase[J]. J Biol Chem.2000,75(40):31444-31450.
[81] Kawaguchi H, Chikazu D, Nakamura K, Direct and indirect actions of fibroblast growthfactor2on osteoclastic bone resorption in cultures[J]. J Bone Miner Res.2000,15(3):466-473.
[82] Purushothaman R, Cox TC, Muga AM, etal.Facial suture synostosis of newborn Fgfr1(P250R/+) and Fgfr2(S252W/+) mouse models of Pfeiffer and Apert syndromes[J].Birth Defects Res A Clin Mol Teratol.2011,91(7):603-609.
[83] Wilkie AO, Oldridge M, Tang Z,etal.Craniosynostosis and related limb anomalies.Novartis Found Symp.[J].2001,232:122-133.
[84] Bent Bone Dysplasia-FGFR2type, a Distinct Skeletal Disorder, Has Deficient Canoni-cal FGF Signaling[J]. Am J Hum Genet.2012,90(3):550-557.
[85] Brodie SG, Deng CX.Mouse models orthologous to FGFR3-related skeletal dysplasias[J]. Pediatr Pathol Mol Med.2003,22(1):87-103.
[86]陈莹、林崇韬、高颖.碱性成纤维细胞生长因子对牙周膜细胞表皮生长因子受体基因表达的影响[J].华西口腔医学杂志2009,27,(3):340-342.
[87]张韶君、梁益慧、杨丕山。碱性成纤维细胞生长因子对人牙周膜细胞生长的影响[J].上海口腔医学2001,10(2):135-137.
[88] Lee JH, Um S, Jang JH, etal. Effects of VEGF and FGF-2on proliferation and differe-ntiation of human periodontal ligament stem cells[J]. Cell Tissue Res.2012,3.[Epubahead of print]
[89] Asakawa T, Chosa N, Yoshimura Yetal.Fibroblast growth factor2inhibits the expressionofstromal cell-derived factor1α in periodontal ligament cells derived from humanpermanent teeth in vitro[J].. Int J Mol Med.2012,9(4):569-573.
[90] Seshima F, Ota M, Kinumatsu T,Effect of recombinant basic fibroblast growth factor onreimplanted teeth in beagle dogs[J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.2010,09(1):142-148.
[91] Takahashi M, Okubo N, Chosa N, etal.Fibroblast growth factor-1-induced ERK1/2signaling reciprocally regulates proliferation and smooth muscle cell differentiation ofligament-derived endothelial progenitor cell-like cells[J]. Int J Mol Med.2012,9(3):357-364.
[92]程敏、刘晓红、程琳等。碱性成纤维细胞生长因子在牙发育各阶段中的表达及意义[J].吉林大学学报(医学版)2009,35(5):829-831.
[93] Bailleul-Forestier I, Gros C, Zenaty D etal.Dental agenesis in Kallmann syndromeindividuals with FGFR1mutations.[J]. Int J Paediatr Dent.2010,20(4):305-312.
[94] Linsuwanont B, Takagi Y, Ohya K, etal..Localization of Cathepsin K in BovineOdontoclasts during Deciduous Tooth Resorption[J].Calcif Tissue,2002,70(2):127–133.
[95] Tsuchiya M, Akiba Y, Takahashi I, etal.Comparison of expression patterns of cathepsinK and MMP-9in odontoclasts and osteoclasts in physiological root resorption in the ratmolar[J]. Arch Histol Cytol.2008,1(2):89-100.
[96] Okaji M, Sakai H, Sakai E etal.The Regulation of Bone Resorption in Tooth Formationand EruptionProcesses in Mouse Alveolar Crest Devoid of Cathepsin K[J]. JPharmacol Sci,2003,91(4):285-294.
[97] Ishikura Y.A study of root resorption ofdeciduous teeth in dogs. Influence of success-sional tooth germ and occlusal force [J]. Shoni Shikagaku Zasshi.1991,29(1):102-129.
[98] Lin BC, Zhao YM, Ge LH. Root resorption of primary molars without successor teeth.An experimental study in the beagle dog.[J] Eur J Oral Sci.2012,120(2):147-152.
[99] Wise GE, Lin F, Fan W. Localization of epidermal growth factor and its receptor inmandibular molars of the rat prior to and during prefunctional tooth eruption.[J]DevDyn.1992,195(2):121-126.
[100]Wise GE, Frazier-Bowers S, D'Souza RN.Cellular, molecular, and genetic determinantsof tooth eruption.[J] Crit Rev Oral Biol Med.2002,13(4):323-34.
[101]Sahara N.Cellular events at the onset of physiological root resorption in rabbitdeciduous teeth.[J] Anat Rec.2001,64(4):387-396.
[102]Larson EK, Cahill DR, Gorski JP,The effect of removing the true dental follicle onpremolar eruption in the dog.[J]Arch Oral Biol.1994,39(4):271-275.
[103]Cahill DR, Marks SC Jr.Tooth eruption: evidence for the central role of the dentalfollicle. J Oral Pathol.[J]1980,(4):189-200.
[104]Gelb BD, Shi GP, Chapman HA et al.Pycnodysostosis,a lysosomal disease caused bycathepsin K deficiency[J].Science,1996,273(5279):1236–1238.
[105]Hofbauer LC,Khosla S,Dunstan CR,et al.The role of osteoprotegerin andosteoprotegerin ligand in the paracrine regulation of bone resorption[J].bone MinerRes,2000,15(1):2-12.
[106]Jacob AL, Smith C, Partanen J, etal. Fibroblast growth factor receptor1signaling in theosteo-chondrogenic cell lineage regulates sequential steps of osteoblast maturation[J].Dev Biol.2006,296(2):315-328.
[107]Shirai K, Ishisaki A, Kaku T, etal.Multipotency of clonal cells derived from swineperiodontal ligament and differential regulation by fibroblast growth factor and bonemorphogenetic protein[J]. J Periodontal Res.2009,44(2):238-247.
[108]Chan CT, Thorogood P.Pleiotropic features of syndromic craniosynostoses correlatewithdifferential expression of fibroblast growth factor receptors1and2during humancraniofacial development[J].. Pediatr Res.1999,45(1):46-53.
[109]Takamori K, Hosokawa R, Xu X, etal.Epithelial fibroblast growth factor receptor1regulates enamel formation[J]. J Dent Res.2008,87(3):238-43.