Sox9、CTGF及BMP-2对促进腱骨结合处早期愈合的研究Role of Sox9,CTGF and BMP-2 in bone tendon junction healing
李朋;候明;朱智奇;王德桂;林学扬;
摘要(Abstract):
[目的]观察SRY相关高迁移组box基因9蛋白(Sox9)及结缔组织生长因子(CTGF)、骨形态发生蛋白2(BMP-2)在促进腱骨结合处愈合的作用。[方法]72只成年新西兰大白兔随机分为Sox9组、CTGF组、BMP-2组及对照组。Sox9组、CTGF组、BMP-2组分别于骨与肌腱的缝合处注入浓度为200 ng/ml的Sox9、CTGF及BMP-2各2 ml,对照组只手术但不注射任何材料。建立动物模型后对四组行动物实验并分别于术后4、8及12周行组织学及生物力学检查,统计学分析结果。[结果]术后第4、8、12周,Sox9组、CTGF组的组织学愈合情况均好于对照组,生物力学分析中Sox9组、CTGF组腱骨愈合界面的横截面积均低于对照组,拉断负荷及极限拉应力均高于对照组(P<0.05),而BMP-2组各项指标均与对照组差异无统计学意义。[结论]Sox9以及CTGF组能够促进腱骨结合处的早期愈合,并能够增加其生物力学强度,而BMP-2对骨肌腱结合部位愈合并无明显作用。
关键词(KeyWords): Sox9;CTGF;BMP-2;腱骨结合
基金项目(Foundation):
作者(Author): 李朋;候明;朱智奇;王德桂;林学扬;
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参考文献(References):
- [1]Jin QU,Andrew R,Thoreson A,et al.Tendon gradient mineralization for tendon to bone interface integration[J].J Orthop Res,2013,11,31(11):1713-1719.
- [2]Lu H,Hu J,Qin L,et al.Area,length and mineralization content of new bone at bone-tendon junction predict its repair quality[J].J Orthop Res,2011,29(5):672-627.
- [3]Nourissat G,Diop A,Maurel N,et al.Mesenchymal stem cell therapy regenerates the native bone-tendon junction after surgical repair in a degenerative rat model[J].PLo S One,2010,18,5(8):12248.
- [4]Woo SLY,Gomez MA,Sites TJ,et al.The biomechanical and morphological changes in the medial collateral ligament of the rabbit after immobilization and remobilization[J].Bone Joint Surg,1987,69:1200-1211.
- [5]Ling Q,Lin W,Margaret WW.Osteogenesis induced by extracorporeal shockwave in treatment of delayed osteotendinous junction healing[J].J Orthop Res,2010,28(1):70-76.
- [6]Dangher E,Hays PL,Kawamura S,et al.Immobilization modulates macrophage accumulation in tendon-bone healing[J].Clin Orthop,2009,467(1):281-287.
- [7]Lu H,Qin L,Cheung W.Low-intensity pulsed ultrasound accelerated bone-tendon junction healing through regulation of vascular endothelial growth factor expression and cartilage formation[J].Ultrasound Med Biol,2008,34(8):1248-1260.
- [8]Helen H,Thomopoulos S.Functional attachment of soft tissues to bone:development,healing,and tissue engineering[J].Annu Rev Biomed Eng,2013,15(1):201-226.
- [9]Genin GM,Kent A,Birman V,et al.Functional grading of mineral and collagen in the attachment of tendon to bone[J].Biophys J,2009,19,97(4):976-985.
- [10]Dynybil C,Kawamura S,Kim HJ,et al.The effect of osteoprote gerin on tendon bone healing after reconstruction of the anterior cruciate ligament:a histomorphological and radiographical study in the rabbit[J].Z Orthop Ihre Grenzgeb,2006,144(2):179-186.
- [11]Wong MW,Qin L,Lee KM,et al.Articular cartilage increases transition zone regeneration in bone-tendon junction healing[J].Clin Orthop,2009,467(4):1092-1100.
- [12]Hays PL,Kawamura S,Deng XH,et al.The role of macrophages in early healing of a tendon graft in a bone tunnel[J].J Bone Joint Surg Am,2008,90(3):565-579.
- [13]Elazar Zelzer,Einat Blitz,Megan L,et al.Tendon-to-bone attachment:from development to maturity[J].Birth Defects Res C Embryo Today,2014,3,102(1):101-112
- [14]Lu MH,Zheng YP,Huang QH,et al.Low intensity pulsed ultrasound increases the mechanical properties of the healing tissues at bonetendon junction[J].Conf Proc IEEE Eng Med Biol Soc,2009,2009:2141-2144.
- [15]Henry SP,Liang SD,Akdemir KC,et al.The postnatal role of Sox9 in cartilage[J].J Bone Miner Res,2012,27(12):2511-2525.
- [16]Zanaria E,Muscatelli F,Bardoni B,et al.An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita[J].Nature,1994,372(6507):635-641.
- [17]Gao Y,Xie M,He ZP.The effect of hypoxia on the expression of RHO/RHO signaling pathway and CTGF of human embryonic fibroblasts[J].Sichuan Da Xue Xue Bao Yi Xue Ban,2010,41(6):946-950.
- [18]Zhang W,Oliver N,Lin A,et al.Cooperative interaction of CTGF and TGF-βin animal models of fibrotic disease[J].Fibrogen Tiss Rep,2011,4(1):4.
- [19]Tache D,Bogdan F,Pisoschi C,et al.Evidence for the involvement of TGF-β1-CTGF axis in liver fibrogenesis secondary to hepatic viral infection[J].Rom J Morphol Embryol,2011,52(1):409-412.
- [20]Wegman F,Bijenhof A,Schuijff L,et al.Osteogenic differentiation as a result of BMP-2 plasmid DNA based gene therapy in vitro and in vivo[J].Eur Cell Mater,2011,15(21):230-242.
- [21]Wulsten D,Glatt V,Ellinghaus A,et al.Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics[J].Eur Cell Mater,2011,21(2):177-192.
- [22]Miguez PA,Terajima M,Nagaoka H,et al.Role of glycosaminoglycans of biglycan in BMP-2 signaling[J].Biochem Biophys Res Commun,2011,405(2):262-266.
- [23]Hamrick MW,Mc Neil PL,Patterson SL.Role of muscle-derived growth factors in bone formation[J].J Musculoskelet Neur Inter,2010,10(1):64-70.
- [24]Zhao J,Zhang P,Qin L,et al.Hypoxia is essential for bone-tendon junction healing:the molecular biological evidence[J].Int Orthop,2010,12(1):3.