DKK-1在颞下颌关节骨关节病中的作用

发布时间：2018-03-27 06:21

本文选题：DKK1　切入点：滑膜　出处：《武汉大学》2015年博士论文

【摘要】：第一部分DKK-1蛋白在骨关节病滑膜中的表达目的：DKK-1在肿瘤、风湿性关节炎等病理过程均发挥着重要作用,本部分研究目的在于探究DKK-1在颞下颌关节骨关节病滑膜中的表达。方法：利用免疫组织化学分别检测DKK-1在颞下颌关节骨关节病滑膜中的表达水平；结果：多数颞下颌关节滑膜组织中均可检测到DKK-1。正常组及骨关节病组的DKK-1的表达部位无明显区别,均表现为胞质和胞核的染色,并且在间质区域亦有稍浅的染色。在染色强度上,骨关节病组的滑膜呈现出明显的颜色加深。骨关节病组深棕色染色,细胞染色多而广泛,而正常滑膜组染色浅,部分细胞不染色。在大血管及新生小血管周围DKK-1表达尤为加强。经统计学分析,骨关节病组DKK-1表达明显强于正常滑膜组。结论：DKK-1蛋白在颞下颌关节骨关节病滑膜中高表达。第二部分DKK-1及VEGF蛋白在颞下颌关节紊乱病关节滑液中表达的表达目的：颞下颌关节滑液中蛋白含量的变化反应了滑膜细胞病理、生理状况。本部分研究目的在于检测颞下颌关节滑液中DKK-1和VEGF的含量,并分析它们的相关性。方法：抽取正常志愿者、颞下颌关节盘移位、骨关节病患者的滑液,利用ELISA检测颞下颌关节滑液中DKK-1及VEGF的含量。结果：DKK-1及VEGF蛋白在颞下颌关节病滑液中高表达,在骨关节病组DKK-1、VEGF的表达水平最高,不可复性关节盘前移位次之,而可复性关节病组在患者人群中DKK-1表达最低,通过相关性分析,DKK-1与VEGF之间的表达呈正相关性结论：DKK-1及VEGF蛋白在颞下颌关节病关节滑液中高表达。DKK-1高表达可能与颞下颌关节病血管生成有关第三部分DKK-1在颞下颌关节滑膜细胞中的表达及作用机制目的：本部分研究目的在于通过颞下颌关节滑膜细胞原代培养,在体外环境中检测DKK-1对于VEGF表达的影响及其机制方法：对炎性环境下颞下颌关节滑膜细胞DKK-1表达进行检测,并分析封闭DKK-1及给予外源性DKK-1后VEGF的表达,采用HIF-1α siRNA干扰后检测外源性DKK-1对VEGF表达的影响。利用条件培养基检测DKK-1对血管内皮细胞系迁移和成管能力的影响。结果：炎性环境中DKK-1及VEGF在颞下颌关节滑膜细胞中表达增加,颞下颌关节滑膜细胞中DKK-1通过上调HIF-1a来调控VEGF的表达,DKK-1对脐静脉内皮细胞HUVECs迁移、成管能力具有上调的作用结论：DKK-1参与调控颞下颌关节滑膜细胞VEGF的表达,并可能与滑膜炎症血管生成有关。
[Abstract]:Part 1 expression of DKK-1 protein in synovial osteoarthritis Objective: DKK-1 in cancer, rheumatoid arthritis and other pathological processes play important roles, the purpose of this part of study is to explore DKK-1 expression in temporomandibular joint osteoarthritis synovium. Methods: the immunohistochemical expression of DKK-1 in temporomandibular joint osteoarthritis in the synovium were detected; results: most of the temporomandibular joint synovial tissue can be detected in the expression site of DKK-1. normal group and osteoarthropathy group DKK-1 showed no significant difference between staining of cytoplasm and nucleus, and in the interstitial region is also stained slightly lighter staining intensity in. On the synovial osteoarthritis group showed obvious color deepened. Bone and joint disease group deep brown staining, cell staining and more widely, and the normal synovial staining shallow, non staining. Some cells in large vessel and newborn Perivascular DKK-1 expression is particularly strengthened. By statistical analysis, bone and joint disease group DKK-1 expression was significantly stronger in normal synovial group. Conclusion: high expression of DKK-1 protein in temporomandibular joint synovial membrane. The second part of DKK-1 and VEGF protein expression in the objective table of temporomandibular disorders: changes of protein content in synovial fluid temporomandibular joint synovial fluid reaction in synovial cell pathological, physiological status. The purpose of this part of study is to detect the level of DKK-1 and VEGF in temporomandibular joint synovial fluid, and analyze their relationship. Methods: from normal volunteers, disc displacement of temporomandibular joint synovial fluid, bone joint disease patients, the contents of DKK-1 and VEGF ELISA detection temporomandibular joint synovial fluid. Results: DKK-1 and VEGF protein expression in temporomandibular joint disease in synovial fluid of osteoarthritis, in group DKK-1, the expression level of VEGF is the highest, the irreducible closed section Anterior disc displacement of temporomandibular joint disease and in patients of DKK-1 group was the lowest, through correlation analysis, the expression of positive correlation between DKK-1 and VEGF. Conclusion: DKK-1 and VEGF protein expression in temporomandibular joint disease in synovial fluid of high expression of.DKK-1 may be associated with temporomandibular joint disease objective function and expression of angiogenesis the third part of the DKK-1 mechanism in the temporomandibular joint synovial cells: the purpose of this part is through the study of temporomandibular joint synovial cells cultured in vitro environment for detection of DKK-1 VEGF expression and its mechanism methods: to detect the expression of inflammatory environment of temporomandibular joint synovial cell DKK-1, and analyze the expression of VEGF the closed DKK-1 and exogenous DKK-1, detect the effect of exogenous DKK-1 on the expression of VEGF by HIF-1 alpha after siRNA interference. Using the conditioned medium for detection of DKK-1 on blood vessels Effect of endothelial cell migration and tube formation. Results: DKK-1 and VEGF expression increased in the inflammatory environment in temporomandibular joint synovial cells in DKK-1 synovial cells by upregulation of HIF-1a in regulating the expression of VEGF, DKK-1, HUVECs on the migration of human umbilical vein endothelial cells, conclusion: tube has the ability to increase the expression of DKK-1 is involved in the regulation of temporomandibular joint synovial cells VEGF, and may be associated with synovitis of angiogenesis.

【学位授予单位】：武汉大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R782.6

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