组织工程骨用于兔腰椎融合的BMP-2表达和显微CT研究
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摘要
目的:观察重组人骨形态发生蛋白-2/异体骨复合骨(组织工程骨)、自体骨与异体骨用于兔腰椎融合后,不同时间点融合骨组织中内源性BMP-2的基因表达和其微结构的变化。方法:成年雄性新西兰大白兔72只,随机分为3组,每组24只。在每只兔的L5、L6横突间行腰椎后路植骨融合术,各组分别植入复合骨条,自体髂骨条以及单纯异体髂骨条,每组于术后第4天、1、2、3、4、5周各处死4只大白兔,分离保存融合节段标本,每份标本随机选择其中一侧融合骨组织用原位杂交法检测其内源性BMP-2的基因表达,另一侧则用显微CT扫描后行骨组织定量分析。结果:术后6个时间点中,复合骨组BMP-2的表达均要高于自体骨组及异体骨组(P<0.05);在第5周时,自体骨组与异体骨组BMP-2的表达差异无统计学意义(P>0.05)。术后第3、4、5周,复合骨组和自体骨组新生骨小梁的质量和形态均要优于异体骨组且差别有统计学意义(P<0.05)。第3周,复合骨组的组织骨密度(TMD)为(433.98±2.64)mg/cm3,高于自体骨组(424.81±4.69)mg/cm3(P<0.05);第4周,复合骨组的骨小梁厚度(Tb.Th)为(0.097±0.004)mm,高于自体骨组(0.082±0.003)mm(P<0.01);第5周,复合组的组织矿含量(TMC)为(7.70±0.30)mg,高于自体骨组(7.00±0.24)mg(P<0.01)。结论:在兔腰椎后路横突间植骨融合中,rhBMP-2/异体骨复合骨能很好的促进骨组织的形成,其成骨效应不低于自体骨,优于异体骨。
Objective: To investigate the endogenous BMP-2 gene expression and the microstructure of fusion masses taken from the rabbits undergone posterolateral lumbar spinal fusion with rhBMP-2/allograft composite, autograft and allograft. Methods: Seventy-two adult male New Zealand white rabbits were randomly divided into three groups: rhBMP-2/allograft composite group, autograft group and allograft group, and each group included 24 rabbits. The rabbits were undergone L5, L6 intertransverse process fusion using rhBMP-2/allograft composite, autogenous iliac crest bone graft and allograft. Every four rabbits from each group sacrificed at the 4 th day and the 1th ,2th ,3th, 4th, 5th week after operation, and the fusion masses were harvested then. One side of each fusion mass was randomly chosen for the use of testing the endogenous BMP-2 gene expression by in situ hybridization, and a high resolution micro CT was used to identify the densimetric and microstructural properties of the other side of the fusion mass. Results: The endogenous BMP-2 gene expression of the composite group was significantly higher than that of autograft group and allograft group at all the six time-points. At the 5th week, there was no significant difference between the autograft group and the allograft group in the endogenous BMP-2 gene expression. Compared with the allograft group at the 3th, 4th, 5th week after operation, there was a significant difference in all parameters in the trabecular bone of the rhBMP-2/allograft composite group and autograft group. At the 3th week, the mean value of Tissue Mineral Density (TMD) in the composite group was (433.98±2.64)mg/cm3, it was significantly higher than that of autograft group(424.81±4.69)mg/cm3. At the 4th week, the mean value of Trabecular Thickness(Tb.Th) in the composite group was(0.097±0.004)mm, it was significantly higher than that of autograft group(0.082±0.003)mm. At the 5th week, the mean value of Tissue Mineral Content(TMC) in the composite group was(7.70±0.30)mg, it was significantly higher than that of autograft group(7.00±0.24)mg. Conclusion: The rhBMP-2/allograft composite was not inferior to autograft and superior to allograft in accelerating and enhancing bone formation in a rabbit posterolateral lumbar spinal fusion model.
Objective: To investigate the endogenous BMP-2 gene expression and the microstructure of fusion masses taken from the rabbits undergone posterolateral lumbar spinal fusion with rhBMP-2/allograft composite, autograft and allograft. Methods: Seventy-two adult male New Zealand white rabbits were randomly divided into three groups: rhBMP-2/allograft composite group, autograft group and allograft group, and each group included 24 rabbits. The rabbits were undergone L5, L6 intertransverse process fusion using rhBMP-2/allograft composite, autogenous iliac crest bone graft and allograft. Every four rabbits from each group sacrificed at the 4 th day and the 1th ,2th ,3th, 4th, 5th week after operation, and the fusion masses were harvested then. One side of each fusion mass was randomly chosen for the use of testing the endogenous BMP-2 gene expression by in situ hybridization, and a high resolution micro CT was used to identify the densimetric and microstructural properties of the other side of the fusion mass. Results: The endogenous BMP-2 gene expression of the composite group was significantly higher than that of autograft group and allograft group at all the six time-points. At the 5th week, there was no significant difference between the autograft group and the allograft group in the endogenous BMP-2 gene expression. Compared with the allograft group at the 3th, 4th, 5th week after operation, there was a significant difference in all parameters in the trabecular bone of the rhBMP-2/allograft composite group and autograft group. At the 3th week, the mean value of Tissue Mineral Density (TMD) in the composite group was (433.98±2.64)mg/cm3, it was significantly higher than that of autograft group(424.81±4.69)mg/cm3. At the 4th week, the mean value of Trabecular Thickness(Tb.Th) in the composite group was(0.097±0.004)mm, it was significantly higher than that of autograft group(0.082±0.003)mm. At the 5th week, the mean value of Tissue Mineral Content(TMC) in the composite group was(7.70±0.30)mg, it was significantly higher than that of autograft group(7.00±0.24)mg. Conclusion: The rhBMP-2/allograft composite was not inferior to autograft and superior to allograft in accelerating and enhancing bone formation in a rabbit posterolateral lumbar spinal fusion model.
引文
[1] Boden SD, Kang J, Harvinder S, et al. Use of recombinant human bone morph- ogenetic protein-2 to achieve posterolateral lumbar spine[J].Spine,2002,27:2662-73.
[2] Mundy GR. Regulation of bone formation by bone morphogenic protein and other growth factors[J].Clinical Orthopaedics and Related Research,1996,323:24-28.
[3] Lane JM. Bone morphogenic protein science and studies[J].J Orthop Trauma,2005,19 (10Suppl):S17-S22.
[4] Aspenberg P, Johnsson E, Thorngren KG. Dose-dependent reduction of bone inductive properties by ethylene oxide[J].J Bone Joint Surg (Br),1990,72:1036-1037.
[5]张滨,闫景龙.骨形态发生蛋白在微小颗粒骨诱导成骨过程中的表达[J].中国矫形外科杂志,2004,08(12):1247-1250.
[6] Younger, van Bezooijen RL, van der Horst g, et al. Bone morphogenetic proteins sti- mulate angiogenesis through osteoblast-derived vascular endothelial growth factor[J]. A.Endocrinology,2000,143:1545.
[7]陈雅娟,张彦定.骨形态发生蛋白的骨诱导活性及其应用研究现状[J].中国药物与临床,2003,3(4):277.
[8]桑宏勋,胡蕴玉,孙怡群,等.环氧乙烷和电离辐射对骨移植材料灭菌效果的对比分析[J].中华外科杂志,1996,34:457-459.
[9]梁绍雄,袁华军.同种异体骨移植修复四肢骨肿瘤切除后大段骨缺损[J].中国骨肿瘤骨病,2006,5(2):101-103.
[10]Sandha HS, Khan SN. Animal model for preclinical assessment of bone morphogen- etic proteins in the spiane[J].Spine,2002,27:32-38.
[11]金黎明,刘万顺,韩宝芹,等.骨缺损治疗方法的研究现状[J].中国临床康复, 2006,10(1):144-146.
[12]Mont MA, Ragland PS, Bridget B, et al. Use of bone morphogenetic proteins for musculoskeletal applications: An overview[J].J Bone Joint Surg Am 2004,86:41-55.
[13]Urist MR. Bone formation by auto induction[J].Science,1965,150:893-899.
[14]Cowan CM, Soo C, Ting K, et al. Evolving concepts in bone tissue engineering[J]. Curr Top Dev Biol,2005,66:239-285.
[15]Rodeo SA, Hidaka C, Maher SA. What's new in orthopaedic research[J].J Bone Joint Surg Am,2005,87:2356-2365.
[16]Termaat MF, Den Boer FC, Bakker FC, et al. Bone morphogenetic proteins: Develo-pment and clinical efficacy in the treatment of fractures and bone defects[J]. J Bone Joint Surg Am,2005,87:1367-1378.
[17]彭吾训,龚跃昆,李世和,等.BMP在骨科领域中的临床应用研究进展[J].中华现代临床医学杂志,2005,3(3):215-218.
[18]Campisi P, Hamdy RC, Lauzier D, et al. Overview of the radiology, histology, and bone morphogenetic protein expression during distraction osteogenesis of the man- dible[J].J Otolaryngol,2002,31(5):281-286.
[19]Rodeo SA, Hidaka C, Maher SA. What's new in orthopaedic research[J].J Bone Joint Surg Am,2005,87:2356-2365.
[20]Langer R, Vacanti JP. Tissue engineering[J].Science,1993,260(5110):920-926.
[21]Edwards RB, Seeherman HJ, Bogdanske JJ, et al. Percutaneous injection of recom- binant human bone morphogenetic protein-2 in a calcium phosphate paste accelerates healing of a canine tibial osteotomy[J].J Bone Joint Surg Am,2004,86:14 25-1438.
[22]McErlain DD, Chhem RK, Bohay RN, et al. Micro- computed tomography of a 500- year-old tooth: technical note[J].Can Assoc Radiol,2004,55:242-245.
[23]Ito M, Nishida A, Aoyagi K, et al. Effects of risedronate on trabecular microstructure and biomechanical properties in ovariectomized rat tibia[J].Osteoporos Int,2005,16: 1042-1048.
[24]A.Odgaard, H.J.G. Gundersen. Quantification of connectivity in cancellous bone, with special emphasis on 3-D reconstruction [J].Bone,1993,14:173-182.
[25]Lieberman JR, Daluiski A, Einhorn TA. The role of growth factors in the repair of bone. Biology and Clinical Applications[J].Bone Joint Surg Am,2002,84-A(6):1032- 1044.
[26]熊卉,张伟,邓益辉,等.脱钙冻干异体骨移植对骨缺损的修复作用[J].中华实验外科杂志.2006,23:1547-1548.
[27]李旭升,胡蕴玉,范宏斌,等.组织工程骨软骨复合物的构建与形态学观察[J].中华实验外科杂志,2005,22:284-286.
[28]Bonab MM, Alimoghaddam K, Talebian F, et al. Aging of mesenchymal stem cell in vitro[J].BMC Cell Biol,2006,7:14.
[29]Feldkamp LA, Goldstein SA, Parfitt AM, et al. The direct examination of three- dimensional bone architecture in vitro by computed tomography[J].Bone Miner Re- s,1989,4:3-11.
[30]Nuzzo S, Lafage-Proust MH, Martin-Badosa E, et al. Synchrotron radiation microto- mography allows the analysis of three-dimensional microarchitecture and degree ofmineralization of human iliac crest biopsy specimens effects of etidronate treatment [J].Bone Miner Res,2002,17:1372-1382.
[31]Wang EA, Rosen V, D’Alessandro JS, et al. Recombinant human bone morphogenetic protein induces bone formation[J].Proc Natl Sci Acad USA,1990,87(6):2220-2224.
[32]曾中华,余黎,龚玲玲,等.骨折愈合过程中BMP-2和VEGF的表达[J].武汉大学学报(医学版),2005,26:467-469.
[33]赵剑,谭军,赵敦炎,等.脊柱后外侧融合过程中BMP-2、BMP-4基因的动态表达[J].中国脊柱脊髓杂志,2004,14:414-416.
[34]陈伟富,洪正华.rhBMP-2与脊柱融合[J].实用医学杂志,2007,23(21):3453-3455.
[35]David JB, Richard DF, Subburaman. Growth factors to stimulate bone formation [J].Bone Miner Res,1993,8(suppl2):S565-572.
[36]David W, Holdsworth, Michael M, et al. Micro-CT in small animal and specimen imaging[J].Trends in Biotechnology,2002,20(8):S34-S39.
[37]Samartzis D, Khanna N, Shen FH, et al. Update on bone morphogenetic proteins and their application in spine surgery[J].J Am Coll Surg,2005,200:236-248.
[38]Shields LB, Raque GH, Glassman SD, et al. Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion[J].Spine,2006,31:542-547.
[39]Smucker JD, Rhee JM, Singh K, et al. Increased swelling complications associated with off-label usage of rhBMP-2 in the anterior cervical spine[J].Spine, 2006,3 1:2813-2819.
[40]McClellan JW, Mulconrey DS, Forbes RJ, et al. Vertebral bone resorption after trans- foraminal lumbar interbody fusion with bone morphogenetic protein (rhBMP-2)[J].J Spinal Disord Tech,2006,19:483-486.
[41]Fiorellini J, Howell T, Cochran D, et al. Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation[J].J Period- ontol,2005,76:605-613.
[42]Kim DJ, Moon SH, Kim H, et al. Bone morphogenetic protein-2 facilitates expression of chondrogenic, not osteogenic, phenotype of human intervertebral disc cells[J].Spin- e,2003,28:2679-84.
[43]Boden SD, Kang J, Harvinder S, et al. Use of recombinant human bone morphoge- netic protein-2 to achieve posterolateral lumbar spine[J].Spine,2002,27: 2662-73.
[44]李建军,王文军,韩冬,等.转染骨形态发生蛋白-2基因的人骨髓间质干细胞复合异种骨支架异位成骨的效果[J].中华创伤杂志,2004,206:347.
[45]王瑞,赵建宁,吴苏稼.关节软组织工程修复的支架材料[J].医学研究生学报,2006,196:561-564.
[46]宁志杰.骨科临床新进展[M].北京:人民军医出版社,2003:384-436.
[47]张民,卢汉生,杜靖远.骨形态发生蛋白复合同种松质骨载体修复节段性骨缺损的实验研究[J].实用骨科杂志,2004,10(3):219-221.
[48]鱼兵,闫露,范清宇,等.人及基因共表达腺病毒的构建及在兔BMP-7,VEGF骨髓基质干细胞中的共表达[J].中国矫形外科杂志,2004,12(21-22):1704-1707.
[49]周光新,施鑫,吴苏稼,等.骨形态发生蛋白在大段同种异体骨移植中的表达[J].中国组织工程研究与临床康复,2007,11(4):625-628.
[50]赵建宁,吴苏稼.骨形态发生蛋白在同种异体骨移植中的基因表达[J].中国组织工程研究与临床康复,2006,11(4):621-623.
[51]杨树青,王志强,张志刚,等.骨形态发生蛋白在骨修复中的应用[J].中国临床康复, 2006,10(17):146-148.
[52]Glassman SD, Dimar JR, Carreon LY, et al. Initial fusion rates with recombinant hu- man bone morphogenetic protein-2/compression resistant matrix and a hydroxyapatite and tricalcium phosphate/collagen carrier in posterolateral spinal fusion[J].Spin- e,2005,30:1694-8.
[53]盛志峰,廖二元,伍贤平,等.去卵巢大鼠胫骨骨小梁的显微CT研究[J].中华骨科杂志,2007,27(6):460-464.
[1] Lieberman JR, Daluiski A, Einhorn TA. The role of growth factors in the repair of bone. Biology and clinical applications[J].J Bone Joint Surg Am,2002,84-A(6):1032- 1044.
[2] Urist MR. Bone formation by autoinduction[J].Science,1965,150:893-9.
[3] Sciadini MF, Johnson KD. Evaluation of recombinant human bone morphogenetic protein-2 as a bone-graft substitute in a canine segmental defect model[J].J Orthop Res,2000,18(2):289-302.
[4] Bouxsein ML, Turek TJ , Blake CA, et al. Recombinant human bone morphogenetic protein-2 accelerates healing in a rabbit ulnar osteotomy model[J].J Bone Joint Surg Am,2001,83-A(8):1219-1230.
[5] Li RH, Bouxsein ML, Blake CA, et al. rhBMP-2 injected in a calcium phosphate paste (alpha-BSM) accelerates healing in the rabbit ulnar osteotomy model[J].J Orthop Res,2003,21(6):997-1004.
[6] Granjeiro JM, Oliveira RC, Bustos-Valenzuela JC, et al. Bone morphogenetic proteins: from structure to clinical use[J].J Brazilian Journal of Medical and Biological Research, 2005,38:1463-1473.
[7] Wang EA, Rosen B, D' Alessandro JS, et al. Recombinant human bone morphogenetic protein induces bone formation[J]. Proc Natl Acad Sci USA,1990,87:2220-4.
[8] Ozkaynak E, Rueger DC, Drier EA, et al. OP-1 cDNA encodes an ostegenic protein in the TGF-βfamily[J]. Eur Mol Biol Organ J,1990,9:2085-93.
[9] Boden SD, Schimandle JH, Hutton WC. The use of an osteoinductive growth factor for lumbar spinal fusion, Part II: Study of dose, carrier, and species[J].Spine, 1995,20:26 33-44.
[10]Fang J, Zhu Y, Smiley E, et al. Stimulation of new bone formation by direct transfer of osteogenic plasmid genes.Proc Natl Acad Sci USA,1996,93:5753-8.
[11]Croteau S, Rauch F, Silvestri A, et al. Bone morphogenetic proteins in orthopedics: from basic science to clinical practice[J].Orthopedics,1999,22(7):686.
[12]Valentin-Opran A, Wozney J, Csimma C, et al. Clinical evaluation of recombinant human bone morphogenetic protein-2.Clin Orthop Relat Res,2002,(395):110-20.
[13]Murakami N, Saito N, Horiuchi H, et al. Repair of segmental defects in rabbit humeri with titanium fiber mesh cylinders containing recombinant human bone morphogenetic protein-2 (rhBMP-2) and a synthetic polymer[J].J Biomed Maler Res,2002,62(2):169-74.
[14]张永刚,卢世璧,王继芳.骨引导与骨诱导[J].中华创伤杂志,1996,31(1):199-209.
[15]Bahamonde, Matthew E, Lyons Karen M. BMP23: To Be or Not To Be a BMP [J].J Bone Joint Surg Am,2001,832A ( Supp11):56-62.
[16]Kuebler N, Urist M.Cell differentiation in response to partielly purified osteosarcoma- derived bone morphogenetic protein in vivo and in vitro[J].Clin Orthop,1993,292:321- 328.
[17]Reddi AH. Bone morphogenetic proteins, bone marrow stromal cells, and mesen- chymal stem cells[J].Clin Orthop,2003,(313):115-119.
[18]John M. Wozney PhD. Overview of bone morphorgenetic protein[J].Spine,2002, 27:s2-8.
[19]Ebara S, Nakayama K. Mechanism for the action of bone morphogenic proteins and regulation of their activity[J].Spine,2002,27:S10-15.
[20]Hay E, Hott M, Graulet AM, et al. Graulet AM et al.Effects of bone morpho-genetic protein-2on human neonatal calvaria cell differentiation[J].J Cell Biochem,1999,72 (1):81-93.
[21]Noshi T, Yoshikawa T, Dohi Y, et al. Recombinant human bone morphogenetic protein-2 potentiates the in vivo osteogenic ability of marrow/hydroxyapatite compos- ites[J].Artificial Organs,2001,25:201-208.
[22]Musgrave DS, Bosch P, Lee JY. et al. Ex vivo gene therapy to produce bone using different cell types[J].Clin Orthop,2000,378:290-305.
[23]Partridge K, Yang X, Clarke NM, et al. Adenoviral BMP-2 gene transfer in mesen- chymal stem cells: in vitro and in vivo bone formation on biodegradable polymer sca- ffoldds[J].Biochem Biophys Res Cummun,2002,292(1):144-152.
[24]Lu HH, Kofron MD, El-Amin SF, et al. In vitro bone formation using musde-derived cells:a new paradigm for bone tissue engineering using polymer-bone morphogenetic protein matrices[J].Biochem Biophys Res Commun,2003, 305(4):882-889.
[25]zur Nieden NI, Kempka G, Rancourt DE, et al. Induction of chondro-, osteo- and adipogenesis in embryonic stem cells by bone morphogenetic protein-2: Effect of co-factors on differentiating lineages[J].BMC Dev Biol.2005,5(1):1-15.
[26]Govender S, Csimma C, Genant HK, et al. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients[J].J Bone Joint Surg Am, 2002,84:2123–34.
[27]Baskin DS, Ryan P, Sonntag V, et al. A prospective, randomized, controlled cervicalfusion study using recombinant human bone morphogenetic protein-2 with the corners- tone-SR allograph ring and the Atlantis anterior cervical plate[J].Spine, 2003,28:12 19-25.
[28]Einhorn TA. Clinical applications of recombinant human BMPs: Early experience and future development[J].J Bone Joint Surg Am,2003,85-A(Suppl 3):82–88.
[29]Pradhan BB, Bae HW, Dawson EG, et al. Graft resorption with the use of bone morphogenetic protein: lessons from anterior lumbar interbody fusion using femoral ring allografts and recombinant human bone morphogenetic protein-2[J].Spine, 2006,31:E277–E284.
[30]Burkus JK, Dorchak JD, Sanders DL. Radiographic assessment of interbody fusion using recombinant human bone morphogenetic protein type 2[J].Spine, 2003,28:37 2–7.
[31]Barnes B, Boden SD, Louis-Ugbo J, et al. Lower dose of rhBMP-2 achieves spine fusion when combined with an osteoconductive bulking agent in non-human primates[J].Spine,2005,30:1127–33.
[32]Hidaka C, Goshi K, Rawlins B, et al. Enhancement of spine fusion using combined gene therapy and tissue engineering BMP-7-expressing bone marrow cells and allograft bone[J].Spine,2003,28:2049-57.
[2] Mundy GR. Regulation of bone formation by bone morphogenic protein and other growth factors[J].Clinical Orthopaedics and Related Research,1996,323:24-28.
[3] Lane JM. Bone morphogenic protein science and studies[J].J Orthop Trauma,2005,19 (10Suppl):S17-S22.
[4] Aspenberg P, Johnsson E, Thorngren KG. Dose-dependent reduction of bone inductive properties by ethylene oxide[J].J Bone Joint Surg (Br),1990,72:1036-1037.
[5]张滨,闫景龙.骨形态发生蛋白在微小颗粒骨诱导成骨过程中的表达[J].中国矫形外科杂志,2004,08(12):1247-1250.
[6] Younger, van Bezooijen RL, van der Horst g, et al. Bone morphogenetic proteins sti- mulate angiogenesis through osteoblast-derived vascular endothelial growth factor[J]. A.Endocrinology,2000,143:1545.
[7]陈雅娟,张彦定.骨形态发生蛋白的骨诱导活性及其应用研究现状[J].中国药物与临床,2003,3(4):277.
[8]桑宏勋,胡蕴玉,孙怡群,等.环氧乙烷和电离辐射对骨移植材料灭菌效果的对比分析[J].中华外科杂志,1996,34:457-459.
[9]梁绍雄,袁华军.同种异体骨移植修复四肢骨肿瘤切除后大段骨缺损[J].中国骨肿瘤骨病,2006,5(2):101-103.
[10]Sandha HS, Khan SN. Animal model for preclinical assessment of bone morphogen- etic proteins in the spiane[J].Spine,2002,27:32-38.
[11]金黎明,刘万顺,韩宝芹,等.骨缺损治疗方法的研究现状[J].中国临床康复, 2006,10(1):144-146.
[12]Mont MA, Ragland PS, Bridget B, et al. Use of bone morphogenetic proteins for musculoskeletal applications: An overview[J].J Bone Joint Surg Am 2004,86:41-55.
[13]Urist MR. Bone formation by auto induction[J].Science,1965,150:893-899.
[14]Cowan CM, Soo C, Ting K, et al. Evolving concepts in bone tissue engineering[J]. Curr Top Dev Biol,2005,66:239-285.
[15]Rodeo SA, Hidaka C, Maher SA. What's new in orthopaedic research[J].J Bone Joint Surg Am,2005,87:2356-2365.
[16]Termaat MF, Den Boer FC, Bakker FC, et al. Bone morphogenetic proteins: Develo-pment and clinical efficacy in the treatment of fractures and bone defects[J]. J Bone Joint Surg Am,2005,87:1367-1378.
[17]彭吾训,龚跃昆,李世和,等.BMP在骨科领域中的临床应用研究进展[J].中华现代临床医学杂志,2005,3(3):215-218.
[18]Campisi P, Hamdy RC, Lauzier D, et al. Overview of the radiology, histology, and bone morphogenetic protein expression during distraction osteogenesis of the man- dible[J].J Otolaryngol,2002,31(5):281-286.
[19]Rodeo SA, Hidaka C, Maher SA. What's new in orthopaedic research[J].J Bone Joint Surg Am,2005,87:2356-2365.
[20]Langer R, Vacanti JP. Tissue engineering[J].Science,1993,260(5110):920-926.
[21]Edwards RB, Seeherman HJ, Bogdanske JJ, et al. Percutaneous injection of recom- binant human bone morphogenetic protein-2 in a calcium phosphate paste accelerates healing of a canine tibial osteotomy[J].J Bone Joint Surg Am,2004,86:14 25-1438.
[22]McErlain DD, Chhem RK, Bohay RN, et al. Micro- computed tomography of a 500- year-old tooth: technical note[J].Can Assoc Radiol,2004,55:242-245.
[23]Ito M, Nishida A, Aoyagi K, et al. Effects of risedronate on trabecular microstructure and biomechanical properties in ovariectomized rat tibia[J].Osteoporos Int,2005,16: 1042-1048.
[24]A.Odgaard, H.J.G. Gundersen. Quantification of connectivity in cancellous bone, with special emphasis on 3-D reconstruction [J].Bone,1993,14:173-182.
[25]Lieberman JR, Daluiski A, Einhorn TA. The role of growth factors in the repair of bone. Biology and Clinical Applications[J].Bone Joint Surg Am,2002,84-A(6):1032- 1044.
[26]熊卉,张伟,邓益辉,等.脱钙冻干异体骨移植对骨缺损的修复作用[J].中华实验外科杂志.2006,23:1547-1548.
[27]李旭升,胡蕴玉,范宏斌,等.组织工程骨软骨复合物的构建与形态学观察[J].中华实验外科杂志,2005,22:284-286.
[28]Bonab MM, Alimoghaddam K, Talebian F, et al. Aging of mesenchymal stem cell in vitro[J].BMC Cell Biol,2006,7:14.
[29]Feldkamp LA, Goldstein SA, Parfitt AM, et al. The direct examination of three- dimensional bone architecture in vitro by computed tomography[J].Bone Miner Re- s,1989,4:3-11.
[30]Nuzzo S, Lafage-Proust MH, Martin-Badosa E, et al. Synchrotron radiation microto- mography allows the analysis of three-dimensional microarchitecture and degree ofmineralization of human iliac crest biopsy specimens effects of etidronate treatment [J].Bone Miner Res,2002,17:1372-1382.
[31]Wang EA, Rosen V, D’Alessandro JS, et al. Recombinant human bone morphogenetic protein induces bone formation[J].Proc Natl Sci Acad USA,1990,87(6):2220-2224.
[32]曾中华,余黎,龚玲玲,等.骨折愈合过程中BMP-2和VEGF的表达[J].武汉大学学报(医学版),2005,26:467-469.
[33]赵剑,谭军,赵敦炎,等.脊柱后外侧融合过程中BMP-2、BMP-4基因的动态表达[J].中国脊柱脊髓杂志,2004,14:414-416.
[34]陈伟富,洪正华.rhBMP-2与脊柱融合[J].实用医学杂志,2007,23(21):3453-3455.
[35]David JB, Richard DF, Subburaman. Growth factors to stimulate bone formation [J].Bone Miner Res,1993,8(suppl2):S565-572.
[36]David W, Holdsworth, Michael M, et al. Micro-CT in small animal and specimen imaging[J].Trends in Biotechnology,2002,20(8):S34-S39.
[37]Samartzis D, Khanna N, Shen FH, et al. Update on bone morphogenetic proteins and their application in spine surgery[J].J Am Coll Surg,2005,200:236-248.
[38]Shields LB, Raque GH, Glassman SD, et al. Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion[J].Spine,2006,31:542-547.
[39]Smucker JD, Rhee JM, Singh K, et al. Increased swelling complications associated with off-label usage of rhBMP-2 in the anterior cervical spine[J].Spine, 2006,3 1:2813-2819.
[40]McClellan JW, Mulconrey DS, Forbes RJ, et al. Vertebral bone resorption after trans- foraminal lumbar interbody fusion with bone morphogenetic protein (rhBMP-2)[J].J Spinal Disord Tech,2006,19:483-486.
[41]Fiorellini J, Howell T, Cochran D, et al. Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation[J].J Period- ontol,2005,76:605-613.
[42]Kim DJ, Moon SH, Kim H, et al. Bone morphogenetic protein-2 facilitates expression of chondrogenic, not osteogenic, phenotype of human intervertebral disc cells[J].Spin- e,2003,28:2679-84.
[43]Boden SD, Kang J, Harvinder S, et al. Use of recombinant human bone morphoge- netic protein-2 to achieve posterolateral lumbar spine[J].Spine,2002,27: 2662-73.
[44]李建军,王文军,韩冬,等.转染骨形态发生蛋白-2基因的人骨髓间质干细胞复合异种骨支架异位成骨的效果[J].中华创伤杂志,2004,206:347.
[45]王瑞,赵建宁,吴苏稼.关节软组织工程修复的支架材料[J].医学研究生学报,2006,196:561-564.
[46]宁志杰.骨科临床新进展[M].北京:人民军医出版社,2003:384-436.
[47]张民,卢汉生,杜靖远.骨形态发生蛋白复合同种松质骨载体修复节段性骨缺损的实验研究[J].实用骨科杂志,2004,10(3):219-221.
[48]鱼兵,闫露,范清宇,等.人及基因共表达腺病毒的构建及在兔BMP-7,VEGF骨髓基质干细胞中的共表达[J].中国矫形外科杂志,2004,12(21-22):1704-1707.
[49]周光新,施鑫,吴苏稼,等.骨形态发生蛋白在大段同种异体骨移植中的表达[J].中国组织工程研究与临床康复,2007,11(4):625-628.
[50]赵建宁,吴苏稼.骨形态发生蛋白在同种异体骨移植中的基因表达[J].中国组织工程研究与临床康复,2006,11(4):621-623.
[51]杨树青,王志强,张志刚,等.骨形态发生蛋白在骨修复中的应用[J].中国临床康复, 2006,10(17):146-148.
[52]Glassman SD, Dimar JR, Carreon LY, et al. Initial fusion rates with recombinant hu- man bone morphogenetic protein-2/compression resistant matrix and a hydroxyapatite and tricalcium phosphate/collagen carrier in posterolateral spinal fusion[J].Spin- e,2005,30:1694-8.
[53]盛志峰,廖二元,伍贤平,等.去卵巢大鼠胫骨骨小梁的显微CT研究[J].中华骨科杂志,2007,27(6):460-464.
[1] Lieberman JR, Daluiski A, Einhorn TA. The role of growth factors in the repair of bone. Biology and clinical applications[J].J Bone Joint Surg Am,2002,84-A(6):1032- 1044.
[2] Urist MR. Bone formation by autoinduction[J].Science,1965,150:893-9.
[3] Sciadini MF, Johnson KD. Evaluation of recombinant human bone morphogenetic protein-2 as a bone-graft substitute in a canine segmental defect model[J].J Orthop Res,2000,18(2):289-302.
[4] Bouxsein ML, Turek TJ , Blake CA, et al. Recombinant human bone morphogenetic protein-2 accelerates healing in a rabbit ulnar osteotomy model[J].J Bone Joint Surg Am,2001,83-A(8):1219-1230.
[5] Li RH, Bouxsein ML, Blake CA, et al. rhBMP-2 injected in a calcium phosphate paste (alpha-BSM) accelerates healing in the rabbit ulnar osteotomy model[J].J Orthop Res,2003,21(6):997-1004.
[6] Granjeiro JM, Oliveira RC, Bustos-Valenzuela JC, et al. Bone morphogenetic proteins: from structure to clinical use[J].J Brazilian Journal of Medical and Biological Research, 2005,38:1463-1473.
[7] Wang EA, Rosen B, D' Alessandro JS, et al. Recombinant human bone morphogenetic protein induces bone formation[J]. Proc Natl Acad Sci USA,1990,87:2220-4.
[8] Ozkaynak E, Rueger DC, Drier EA, et al. OP-1 cDNA encodes an ostegenic protein in the TGF-βfamily[J]. Eur Mol Biol Organ J,1990,9:2085-93.
[9] Boden SD, Schimandle JH, Hutton WC. The use of an osteoinductive growth factor for lumbar spinal fusion, Part II: Study of dose, carrier, and species[J].Spine, 1995,20:26 33-44.
[10]Fang J, Zhu Y, Smiley E, et al. Stimulation of new bone formation by direct transfer of osteogenic plasmid genes.Proc Natl Acad Sci USA,1996,93:5753-8.
[11]Croteau S, Rauch F, Silvestri A, et al. Bone morphogenetic proteins in orthopedics: from basic science to clinical practice[J].Orthopedics,1999,22(7):686.
[12]Valentin-Opran A, Wozney J, Csimma C, et al. Clinical evaluation of recombinant human bone morphogenetic protein-2.Clin Orthop Relat Res,2002,(395):110-20.
[13]Murakami N, Saito N, Horiuchi H, et al. Repair of segmental defects in rabbit humeri with titanium fiber mesh cylinders containing recombinant human bone morphogenetic protein-2 (rhBMP-2) and a synthetic polymer[J].J Biomed Maler Res,2002,62(2):169-74.
[14]张永刚,卢世璧,王继芳.骨引导与骨诱导[J].中华创伤杂志,1996,31(1):199-209.
[15]Bahamonde, Matthew E, Lyons Karen M. BMP23: To Be or Not To Be a BMP [J].J Bone Joint Surg Am,2001,832A ( Supp11):56-62.
[16]Kuebler N, Urist M.Cell differentiation in response to partielly purified osteosarcoma- derived bone morphogenetic protein in vivo and in vitro[J].Clin Orthop,1993,292:321- 328.
[17]Reddi AH. Bone morphogenetic proteins, bone marrow stromal cells, and mesen- chymal stem cells[J].Clin Orthop,2003,(313):115-119.
[18]John M. Wozney PhD. Overview of bone morphorgenetic protein[J].Spine,2002, 27:s2-8.
[19]Ebara S, Nakayama K. Mechanism for the action of bone morphogenic proteins and regulation of their activity[J].Spine,2002,27:S10-15.
[20]Hay E, Hott M, Graulet AM, et al. Graulet AM et al.Effects of bone morpho-genetic protein-2on human neonatal calvaria cell differentiation[J].J Cell Biochem,1999,72 (1):81-93.
[21]Noshi T, Yoshikawa T, Dohi Y, et al. Recombinant human bone morphogenetic protein-2 potentiates the in vivo osteogenic ability of marrow/hydroxyapatite compos- ites[J].Artificial Organs,2001,25:201-208.
[22]Musgrave DS, Bosch P, Lee JY. et al. Ex vivo gene therapy to produce bone using different cell types[J].Clin Orthop,2000,378:290-305.
[23]Partridge K, Yang X, Clarke NM, et al. Adenoviral BMP-2 gene transfer in mesen- chymal stem cells: in vitro and in vivo bone formation on biodegradable polymer sca- ffoldds[J].Biochem Biophys Res Cummun,2002,292(1):144-152.
[24]Lu HH, Kofron MD, El-Amin SF, et al. In vitro bone formation using musde-derived cells:a new paradigm for bone tissue engineering using polymer-bone morphogenetic protein matrices[J].Biochem Biophys Res Commun,2003, 305(4):882-889.
[25]zur Nieden NI, Kempka G, Rancourt DE, et al. Induction of chondro-, osteo- and adipogenesis in embryonic stem cells by bone morphogenetic protein-2: Effect of co-factors on differentiating lineages[J].BMC Dev Biol.2005,5(1):1-15.
[26]Govender S, Csimma C, Genant HK, et al. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients[J].J Bone Joint Surg Am, 2002,84:2123–34.
[27]Baskin DS, Ryan P, Sonntag V, et al. A prospective, randomized, controlled cervicalfusion study using recombinant human bone morphogenetic protein-2 with the corners- tone-SR allograph ring and the Atlantis anterior cervical plate[J].Spine, 2003,28:12 19-25.
[28]Einhorn TA. Clinical applications of recombinant human BMPs: Early experience and future development[J].J Bone Joint Surg Am,2003,85-A(Suppl 3):82–88.
[29]Pradhan BB, Bae HW, Dawson EG, et al. Graft resorption with the use of bone morphogenetic protein: lessons from anterior lumbar interbody fusion using femoral ring allografts and recombinant human bone morphogenetic protein-2[J].Spine, 2006,31:E277–E284.
[30]Burkus JK, Dorchak JD, Sanders DL. Radiographic assessment of interbody fusion using recombinant human bone morphogenetic protein type 2[J].Spine, 2003,28:37 2–7.
[31]Barnes B, Boden SD, Louis-Ugbo J, et al. Lower dose of rhBMP-2 achieves spine fusion when combined with an osteoconductive bulking agent in non-human primates[J].Spine,2005,30:1127–33.
[32]Hidaka C, Goshi K, Rawlins B, et al. Enhancement of spine fusion using combined gene therapy and tissue engineering BMP-7-expressing bone marrow cells and allograft bone[J].Spine,2003,28:2049-57.
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