消旋聚乳酸复合rhBMP-2/hTGF-β_1诱导小鼠成骨及其机制的研究  

Gene expression and ectopic osteogenesis induced by recombinant human bone morphogenetic protein-2/human transforming growth factor-β_1 delivered in poly-DL-lactic acid

作　　者：王伟[1] 邱蔚六[1] 袁文化[1] 胡勤刚[2] 沈健[3] 陈强[3] 

机构地区：[1]上海第二医科大学附属第九人民医院口腔医学院,上海200011 [2]南京大学附属口腔医院,江苏南京210008 [3]南京大学化学化工学院,江苏南京210093

出　　处：《中国口腔颌面外科杂志》2004年第1期43-47,共5页China Journal of Oral and Maxillofacial Surgery

基　　金：上海市科学技术委员会资助(974119036);上海市教育委员会资助(S970205)

摘　　要：目的:评价消旋聚乳酸(PDLLA)载体材料复合重组rhBMP-2和hTGF-β1诱导小鼠体内异位成骨的能力,初步探讨其作用机制。方法:建立诱导RCI小鼠股部肌内异位成骨的18只动物模型,实验组(各6只)分别植入PDLLA/rhBMP-2/hTGF-β1和PDLLA/rhBMP-2复合材料,对照组(6只)植入PDLLA材料。采用图像处理技术、组织病理学和RT-PCR等分子生物学方法,对消旋聚乳酸载体材料复合2种细胞因子诱导小鼠体内异位成骨能力进行评价;并对其诱导异位成骨过程中,II型胶原蛋白、骨桥蛋白和骨钙蛋白等骨基质蛋白基因表达进行检测。结果:PDLLA/rhBMP-2/hTGF-β1和PDLLA/rhBMP-2组复合材料均具有明显的诱导小鼠肌内异位成骨能力,而单纯PDLLA载体材料无诱导异位成骨能力,表现为小鼠股部复合材料植入区的相对密度指数存在显著性差异。II胶原、骨桥蛋白和骨钙蛋白及其基因在2种细胞因子复合材料植入组中均有较高表达,而在单纯PDLLA组则无表达。结论:PDLLA复合rhBMP-2/hTGF-β1具有诱导异位成骨作用,软骨内成骨是其诱导小鼠体内异位成骨的主要方式。PURPOSE:To evaluate the ability of ectopic osteoinduction of PDDLA/rhBMP-2/hTGF-β 1 compound in mice and investigate the effects of rhBMP-2/hTGF-β 1 on gene expression of collagen-Ⅱ,osteopontin and osteocalcin during ectopic osteogenesis and biomineralization.METHODS:Animal models of ectopic osteogenesis were made with hind limbs of18mice which were classified into3groups,6mice for each group.PDLLA/rhBMP-2/hTGF-β 1 and PDLLA/rhBMP-2were implanted in experiment group,and PDLLA alone was implanted as control group.The opposite hind limbs were regarded as bland control.Macroscope computer-aided image analytical system,histological and molecular biological methods were applied to study the ectopic osteogenesis and gene expression of bone-related extracellular matrix proteins during the process of inducing.RESULTS:PDLLA/rhBMP-2/hTGF-β 1 and PDLLA/rhBMP-2can induce ectopic osteogenesis while PDLLA alone cann't.There was a significant difference of relative density in mice thigh between the experiment and control groups.Gene expression of bone-related extracelluar matrix protein(Ⅱ-type collagen,osteopontin and osteocalcin)were detected in PDLLA/rhBMP-2/hTGF-β 1 and PDLLA/rhBMP-2groups.The intensity of gene expression of osteopontin and osteocalcin in PDLLA/rhBMP-2/hTGF-β 1 group were lower than that of PDLLA/rhBMP-2group,whereas the intensity of gene expression ofⅡ-type collagen in PDLLA/rhBMP-2/hTGF-β 1 group was higher than that of PDLLA/rhBMP-2group.CONCLUSIONS:PDLLA/rhBMP-2/hTGF-β 1 can induce biomineralization during ectopic osteogenesis.Endochondral ossification is the main mode of ectopic osteogenesis in mice.

关 键 词：消旋聚乳酸 生长因子 异位成骨 骨形成蛋白 生物矿化 

分 类 号：R318.08[医药卫生—生物医学工程]