Osteophyte development-molecular characterization of differentiation stages
Osteophyte development-molecular characterization of differentiation stages
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DOI：
10.1053/joca.2002.0873
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发表时间：
2003-02-01
影响因子：
7
通讯作者：
Aigner, T
中科院分区：
文献类型：
--
作者：
Gelse, K;Söder, S;Aigner, T
目的：骨赘是生长在骨关节炎关节边缘的非肿瘤性骨软骨突出物。它们不仅可以被认为是原位修复组织，而且代表了诱导软骨修复过程的良好体内模型。我们的重点是通过分析软骨细胞分化标记基因的表达模式来确定ostophys发育的不同步骤。设计：我们使用组织化学、免疫组织化学和原位杂交技术对基质成分的存在和表达进行了广泛的分析。结果：根据组织形态学和细胞生物学参数可识别骨赘形成的四个不同阶段：从间充质凝聚物开始，以Col2A和聚集蛋白表达的开始为软骨分化阶段（I期）。第二阶段为纤维软骨，其中一方面是软骨和纤维基质成分的混合物，如Col2和聚集蛋白，另一方面是Coll。增殖性骨赘（III期）表现为类似于胎儿生长板软骨的地带性组织，在正在进行的软骨内骨形成区附近有广泛的软骨细胞肥大。“成熟”骨赘（IV期）类似于关节透明软骨，主要存在Col2和聚集蛋白，Col6主要存在于细胞周围。结论：骨赘的发育是成人软骨细胞从多能间充质细胞向原位成熟或增生性软骨细胞分化的良好体内模型。对间充质分化标记分子的分析可以识别修复组织发育的不同阶段以及从纤维组织到新软骨的转变。成熟骨赘的组织结构和基质组成表明，化生的新软骨组织可能是成人关节软骨修复组织的一个潜在来源。(C) 2003年由Elsevier Science Ltd代表国际骨关节炎研究学会出版。
Objective: Osteophytes are non-neoplastic osteo-cartilaginous protrusions growing at the margins of osteoarthritic joints. They can not only be considered as in situ repair tissue, but also represent an excellent in vivo model for induced cartilage repair processes. Our focus was to identify different steps of ostbophyte development via analysis of expression patterns of marker genes of chondrocytic differentiation.Design: We performed an extensive analysis of the presence and expression of matrix components using histochemical, immunohistochemical and in situ hybridization technology.Results: Four different stages of osteophyte formation could be identified based on histomorphological and cell biological parameters: starting from mesenchymal condensates, chondrogenic differentiation is indicated by the onset of Col2A and aggrecan expression (stage I). Stage II shows fibrocartilage with an admixture of cartilaginous and fibrous matrix components such as Col2 and aggrecan on the one hand and Coll on the other hand. The proliferating osteophyte (stage III) shows a zonal organization similar to the fetal growth plate cartilage with extensive chondrocyte hypertrophy in the zones next to ongoing endochondral bone formation. 'Mature' osteophytes (stage IV) resembled largely articular hyaline cartilage with a predominance of Col2 and aggrecan and Col6 found mainly pericellularily.Conclusions: The development of osteophytes is a good in vivo model to pursue chondrocyte differentiation from pluripotent mesenchymal cells to mature or hypertrophic chondrocytes in situ in the adult. The analysis of marker molecules of mesenchymal differentiation allows to identify different stages of repair tissue development and the transformation from fibrous tissue to neo-cartilage. Tissue architecture and matrix composition in mature osteophytes suggests that metaplastic neo-cartilagenous tissue might be one potential source of cartilage repair tissue in the adult joint. (C) 2003 Published by Elsevier Science Ltd on behalf of OsteoArthritis Research Society International.