血小板衍生生长因子-BB在口腔种植领域中的作用
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摘要
组织再生需要生长因子及其类似物、成骨相关细胞、支架材料和良好的血供,其中血小板衍生生长因子(PDGF)是近年来研究和应用较多的一种生长因子,已获得其基因重组产品。PDGF通过激活PDGF受体(PDGFR)对细胞进行调节,现已确定PDGFR-α和PDGFR-β两种PDGFR。PDGF是成骨细胞、成纤维细胞、平滑肌细胞和神经胶质细胞等分裂增殖时重要的促细胞分裂原。小鼠Pdgf基因缺失会致其颈椎骨与肋骨融合或脊柱裂等骨骼畸形,骨折处大量血小板聚集并释放PDGF在内的多种生长因子。在小鼠骨折愈合过程中,PDGF对应的受体也有大量的表达。试验研究显示,PDGF-BB可刺激间质干细胞的增殖和分化,促进骨相关细胞迁移,促进骨组织愈合。临床研究显示,PDGF-BB可促进牙槽骨骨缺损修复,增高牙槽骨,促进种植体周围软组织愈合,治疗种植体周围炎。本文就PDGF-BB在口腔种植治疗中的应用从其结构与功能、试验研究和临床应用等研究进展作一综述。
Bone tissue regeneration engineering involves supplying four basic elements required for bone formation to the defect site,namely,adequate blood supply,bone-forming cells,scaffolds or matrices and signaling molecules,such as growth factors.Platelet-derived growth factor(PDGF) has an important function in organogenesis,development,and trauma healing process,which depend on the binding of the protein tyrosine kinase receptors PDGF receptor-α and β.PDGF is a major mitogen for osteoblasts,fi broblasts,smooth muscle cells,and glial cells.Defects of Pdgf-related genes can lead to skeletal abnormalities,such as fusion of cervical vertebrae and ribs,as well as spina bifi da.Following a fracture,platelets aggregate around the fracture site,which releases PDGF into the developing hematoma.in vitro studies have shown that PDGF promotes proliferation and osteogenicdifferentiation of mesenchymal stem cells,osteoblast migration,and fracture healing.Clinical studies show that PDGF can assist in extract socket and ridge augmentation regeneration,peri-implant soft tissue augmentation,and management of peri-implantitis.This paper reviews the effects of rhPDGF-BB on its structure and functions,experiment research in vivo and in vitro,and clinical trials.
Bone tissue regeneration engineering involves supplying four basic elements required for bone formation to the defect site,namely,adequate blood supply,bone-forming cells,scaffolds or matrices and signaling molecules,such as growth factors.Platelet-derived growth factor(PDGF) has an important function in organogenesis,development,and trauma healing process,which depend on the binding of the protein tyrosine kinase receptors PDGF receptor-α and β.PDGF is a major mitogen for osteoblasts,fi broblasts,smooth muscle cells,and glial cells.Defects of Pdgf-related genes can lead to skeletal abnormalities,such as fusion of cervical vertebrae and ribs,as well as spina bifi da.Following a fracture,platelets aggregate around the fracture site,which releases PDGF into the developing hematoma.in vitro studies have shown that PDGF promotes proliferation and osteogenicdifferentiation of mesenchymal stem cells,osteoblast migration,and fracture healing.Clinical studies show that PDGF can assist in extract socket and ridge augmentation regeneration,peri-implant soft tissue augmentation,and management of peri-implantitis.This paper reviews the effects of rhPDGF-BB on its structure and functions,experiment research in vivo and in vitro,and clinical trials.
引文
[1]Sottosanti JS,Bierly JA.The storage of bone marrow and its relation to periodontal grafting procedures[J].J Periodontol,1975,46(3):162-170.
[2]Blay A,Tunchel S,Sendyk WR.Viability of autogenous bone grafts obtained by using bone collectors:histological and microbiological study[J].Pesqui Odontol Bras,2003,17(3):234-240.
[3]Etcheson AW,Miley DD,Gillespie MJ.Osseous coagulum collected in bone traps:potential for bacterial contamination and methods for decontamination[J].J Oral Implantol,2007,33(3):109-115.
[4]Esposito M,Grusovin MG,Coulthard P,et al.The efficacy of various bone augmentation procedures for dental implants:a Cochrane systematic review of randomized controlled clinical trials[J].Int J Oral Maxillofac Implants,2006,21(5):696-710.
[5]Kaigler D,Avila G,Wisner-Lynch L,et al.Plateletderived growth factor applications in periodontal and peri-implant bone regeneration[J].Expert Opin Biol Ther,2011,11(3):375-385.
[6]Heldin CH,Westermark B.Mechanism of action and in vivo role of platelet-derived growth factor[J].Physiol Rev,1999,79(4):1283-1316.
[7]Andrae J,Gallini R,Betsholtz C.Role of plateletderived growth factors in physiology and medicine[J].Genes Dev,2008,22(10):1276-1312.
[8]Heldin CH,Eriksson U,Ostman A.New members of the platelet-derived growth factor family of mitogens[J].Arch Biochem Biophys,2002,398(2):284-290.
[9]韩为农,彭解英,徐锡萍,等.血小板衍生生长因子BB及其受体在口腔黏膜下纤维化的超微结构定位[J].华西口腔医学杂志,2002,20(4):254-256.
[10]苏牧,刘建国,管晓燕,等.血小板衍生生长因子-BB与胰岛素样生长因子-Ⅰ联合应用对大鼠正畸牙牙周膜细胞整合素β3表达的影响[J].华西口腔医学杂志,2011,29(4):409-412.
[11]Graham S,Leonidou A,Lester M,et al.Investigating the role of PDGF as a potential drug therapy in bone formation and fracture healing[J].Expert Opin Investig Drugs,2009,18(11):1633-1654.
[12]Soriano P.The PDGF alpha receptor is required for neural crest cell development and for normal patterning of the somites[J].Development,1997,124(14):2691-2700.
[13]Mannaioni PF,di Bello MG,Masini E.Platelets and inflammation:role of platelet-derived growth factor,adhesion molecules and histamine[J].Inflamm Res,1997,46(1):4-18.
[14]Slater M,Patava J,Kingham K,et al.Involvement of platelets in stimulating osteogenic activity[J].J Orthop Res,1995,13(5):655-663.
[15]Claesson-Welsh L,Heldin CH.Platelet-derived growth factor.Three isoforms that bind to two distinct cell surface receptors[J].Acta Oncol,1989,28(3):331-334.
[16]Pountos I,Georgouli T,Henshaw K,et al.The effect of bone morphogenetic protein-2,bone morphogenetic protein-7,parathyroid hormone,and plateletderived growth factor on the proliferation and osteogenic differentiation of mesenchymal stem cells derived from osteoporotic bone[J].J Orthop Trauma,2010,24(9):552-556.
[17]Vordemvenne T,Paletta JR,Hartensuer R,et al.Cooperative effects in differentiation and proliferation between PDGF-BB and matrix derived synthetic peptides in human osteoblasts[J].BMC Musculoskelet Disord,2011,12:263.
[18]Ren Y,Yu L,Fan J,et al.Phosphorylation of GIT1tyrosine 321 is required for association with FAK at focal adhesions and for PDGF-activated migration of osteoblasts[J].Mol Cell Biochem,2012,365(1/2):109-118.
[19]Yoshida S,Iwasaki R,Kawana H,et al.PDGFBB promotes PDGFRα-positive cell migration into artificial bone in vivo[J].Biochem Biophys Res Commun,2012,421(4):785-789.
[20]Simion M,Nevins M,Rocchietta I,et al.Vertical ridge augmentation using an equine block infused with recombinant human platelet-derived growth factor-BB:a histologic study in a canine model[J].Int J Periodontics Restorative Dent,2009,29(3):245-255.
[21]Bordei P.Locally applied platelet-derived growth factor accelerates fracture healing[J].J Bone Joint Surg Br,2011,93(12):1653-1659.
[22]Thoma DS,Jung RE,H?nseler P,et al.Impact of recombinant platelet-derived growth factor BB on bone regeneration:a study in rabbits[J].Int J Periodontics Restorative Dent,2012,32(2):195-202.
[23]Nevins ML,Camelo M,Schupbach P,et al.Human buccal plate extraction socket regeneration with recombinant human platelet-derived growth factor BB or enamel matrix derivative[J].Int J Periodontics Restorative Dent,2011,31(5):481-492.
[24]McAllister BS,Haghighat K,Prasad HS,et al.Histologic evaluation of recombinant human plateletderived growth factor-BB after use in extraction socket defects:a case series[J].Int J Periodontics Restorative Dent,2010,30(4):365-373.
[25]Simion M,Rocchietta I,Dellavia C.Threedimensional ridge augmentation with xenograft and recombinant human platelet-derived growth factorBB in humans:report of two cases[J].Int J Periodontics Restorative Dent,2007,27(2):109-115.
[26]de Angelis N,Scivetti M.Lateral ridge augmentation using an equine flex bone block infused with recombinant human platelet-derived growth factor BB:a clinical and histologic study[J].Int J Periodontics Restorative Dent,2011,31(4):383-388.
[27]Urban I,Caplanis N,Lozada JL.Simultaneous vertical guided bone regeneration and guided tissue regeneration in the posterior maxilla using recombinant human platelet-derived growth factor:a case report[J].J Oral Implantol,2009,35(5):251-256.
[28]Bates C,Marino V,Fazzalari NL,et al.Soft tissue attachment to titanium implants coated with growth factors[J].Clin Implant Dent Relat Res,2013,15(1):53-63.
[29]Fagan MC,Miller RE,Lynch SE,et al.Simultaneous augmentation of hard and soft tissues for implant site preparation using recombinant human plateletderived growth factor:a human case report[J].Int J Periodontics Restorative Dent,2008,28(1):37-43.
[30]Simion M,Rocchietta I,Fontana F,et al.Evaluation of a resorbable collagen matrix infused with rhPDGF-BB in peri-implant soft tissue augmentation:a preliminary report with 3.5 years of observation[J].Int J Periodontics Restorative Dent,2012,32(3):273-282.
[31]Froum SJ,Froum SH,Rosen PS.Successful management of peri-implantitis with a regenerative approach:a consecutive series of 51 treated implants with 3-to 7.5-year follow-up[J].Int J Periodontics Restorative Dent,2012,32(1):11-20.
[32]Jayakumar A,Rajababu P,Rohini S,et al.Multicentre,randomized clinical trial on the effi cacy and safety of recombinant human platelet-derived growth factor with beta-tricalcium phosphate in human intra-osseous periodontal defects[J].J Clin Periodontol,2011,38(2):163-172.
[2]Blay A,Tunchel S,Sendyk WR.Viability of autogenous bone grafts obtained by using bone collectors:histological and microbiological study[J].Pesqui Odontol Bras,2003,17(3):234-240.
[3]Etcheson AW,Miley DD,Gillespie MJ.Osseous coagulum collected in bone traps:potential for bacterial contamination and methods for decontamination[J].J Oral Implantol,2007,33(3):109-115.
[4]Esposito M,Grusovin MG,Coulthard P,et al.The efficacy of various bone augmentation procedures for dental implants:a Cochrane systematic review of randomized controlled clinical trials[J].Int J Oral Maxillofac Implants,2006,21(5):696-710.
[5]Kaigler D,Avila G,Wisner-Lynch L,et al.Plateletderived growth factor applications in periodontal and peri-implant bone regeneration[J].Expert Opin Biol Ther,2011,11(3):375-385.
[6]Heldin CH,Westermark B.Mechanism of action and in vivo role of platelet-derived growth factor[J].Physiol Rev,1999,79(4):1283-1316.
[7]Andrae J,Gallini R,Betsholtz C.Role of plateletderived growth factors in physiology and medicine[J].Genes Dev,2008,22(10):1276-1312.
[8]Heldin CH,Eriksson U,Ostman A.New members of the platelet-derived growth factor family of mitogens[J].Arch Biochem Biophys,2002,398(2):284-290.
[9]韩为农,彭解英,徐锡萍,等.血小板衍生生长因子BB及其受体在口腔黏膜下纤维化的超微结构定位[J].华西口腔医学杂志,2002,20(4):254-256.
[10]苏牧,刘建国,管晓燕,等.血小板衍生生长因子-BB与胰岛素样生长因子-Ⅰ联合应用对大鼠正畸牙牙周膜细胞整合素β3表达的影响[J].华西口腔医学杂志,2011,29(4):409-412.
[11]Graham S,Leonidou A,Lester M,et al.Investigating the role of PDGF as a potential drug therapy in bone formation and fracture healing[J].Expert Opin Investig Drugs,2009,18(11):1633-1654.
[12]Soriano P.The PDGF alpha receptor is required for neural crest cell development and for normal patterning of the somites[J].Development,1997,124(14):2691-2700.
[13]Mannaioni PF,di Bello MG,Masini E.Platelets and inflammation:role of platelet-derived growth factor,adhesion molecules and histamine[J].Inflamm Res,1997,46(1):4-18.
[14]Slater M,Patava J,Kingham K,et al.Involvement of platelets in stimulating osteogenic activity[J].J Orthop Res,1995,13(5):655-663.
[15]Claesson-Welsh L,Heldin CH.Platelet-derived growth factor.Three isoforms that bind to two distinct cell surface receptors[J].Acta Oncol,1989,28(3):331-334.
[16]Pountos I,Georgouli T,Henshaw K,et al.The effect of bone morphogenetic protein-2,bone morphogenetic protein-7,parathyroid hormone,and plateletderived growth factor on the proliferation and osteogenic differentiation of mesenchymal stem cells derived from osteoporotic bone[J].J Orthop Trauma,2010,24(9):552-556.
[17]Vordemvenne T,Paletta JR,Hartensuer R,et al.Cooperative effects in differentiation and proliferation between PDGF-BB and matrix derived synthetic peptides in human osteoblasts[J].BMC Musculoskelet Disord,2011,12:263.
[18]Ren Y,Yu L,Fan J,et al.Phosphorylation of GIT1tyrosine 321 is required for association with FAK at focal adhesions and for PDGF-activated migration of osteoblasts[J].Mol Cell Biochem,2012,365(1/2):109-118.
[19]Yoshida S,Iwasaki R,Kawana H,et al.PDGFBB promotes PDGFRα-positive cell migration into artificial bone in vivo[J].Biochem Biophys Res Commun,2012,421(4):785-789.
[20]Simion M,Nevins M,Rocchietta I,et al.Vertical ridge augmentation using an equine block infused with recombinant human platelet-derived growth factor-BB:a histologic study in a canine model[J].Int J Periodontics Restorative Dent,2009,29(3):245-255.
[21]Bordei P.Locally applied platelet-derived growth factor accelerates fracture healing[J].J Bone Joint Surg Br,2011,93(12):1653-1659.
[22]Thoma DS,Jung RE,H?nseler P,et al.Impact of recombinant platelet-derived growth factor BB on bone regeneration:a study in rabbits[J].Int J Periodontics Restorative Dent,2012,32(2):195-202.
[23]Nevins ML,Camelo M,Schupbach P,et al.Human buccal plate extraction socket regeneration with recombinant human platelet-derived growth factor BB or enamel matrix derivative[J].Int J Periodontics Restorative Dent,2011,31(5):481-492.
[24]McAllister BS,Haghighat K,Prasad HS,et al.Histologic evaluation of recombinant human plateletderived growth factor-BB after use in extraction socket defects:a case series[J].Int J Periodontics Restorative Dent,2010,30(4):365-373.
[25]Simion M,Rocchietta I,Dellavia C.Threedimensional ridge augmentation with xenograft and recombinant human platelet-derived growth factorBB in humans:report of two cases[J].Int J Periodontics Restorative Dent,2007,27(2):109-115.
[26]de Angelis N,Scivetti M.Lateral ridge augmentation using an equine flex bone block infused with recombinant human platelet-derived growth factor BB:a clinical and histologic study[J].Int J Periodontics Restorative Dent,2011,31(4):383-388.
[27]Urban I,Caplanis N,Lozada JL.Simultaneous vertical guided bone regeneration and guided tissue regeneration in the posterior maxilla using recombinant human platelet-derived growth factor:a case report[J].J Oral Implantol,2009,35(5):251-256.
[28]Bates C,Marino V,Fazzalari NL,et al.Soft tissue attachment to titanium implants coated with growth factors[J].Clin Implant Dent Relat Res,2013,15(1):53-63.
[29]Fagan MC,Miller RE,Lynch SE,et al.Simultaneous augmentation of hard and soft tissues for implant site preparation using recombinant human plateletderived growth factor:a human case report[J].Int J Periodontics Restorative Dent,2008,28(1):37-43.
[30]Simion M,Rocchietta I,Fontana F,et al.Evaluation of a resorbable collagen matrix infused with rhPDGF-BB in peri-implant soft tissue augmentation:a preliminary report with 3.5 years of observation[J].Int J Periodontics Restorative Dent,2012,32(3):273-282.
[31]Froum SJ,Froum SH,Rosen PS.Successful management of peri-implantitis with a regenerative approach:a consecutive series of 51 treated implants with 3-to 7.5-year follow-up[J].Int J Periodontics Restorative Dent,2012,32(1):11-20.
[32]Jayakumar A,Rajababu P,Rohini S,et al.Multicentre,randomized clinical trial on the effi cacy and safety of recombinant human platelet-derived growth factor with beta-tricalcium phosphate in human intra-osseous periodontal defects[J].J Clin Periodontol,2011,38(2):163-172.