Development of in vitro model of bone destruction by cultured rheumatoid synovium and its inhibition

Osteoclasts，人类组织中的骨骼分解细胞，可能会在风湿性骨毁灭过程中被卷入。为了测试这一催眠，我们开发了一个由骨体类似细胞衍生出来的体外骨骼破坏模型，而不使用任何工业家。当一片风湿性合成蛋白质的材料在盘子、纤维块和宏观细胞上被培养成类似细胞的细胞，从这些材料中提取出来，并在淋巴细胞的共存中繁殖。在培养后14天内，多核细胞出现了富含叶酸酸磷酸酶活性。这些细胞表达了真空HI-D1 + HI-D1-ATPase、维生素受体和Cathepsin K。Although（D1125）|[D1]-鲑鱼钙素绑定非常低，因为细胞含有F-活性素的环形结构，并展示了象牙切片上的强骨骼重建活动。巨噬细胞样细胞的增殖和多核细胞的形成在纤维样细胞的存在中持续了6个月的培养。从风湿性关节炎合成性组织中提取的多核细胞的骨骼重建活动远远高于骨关节炎合成性组织中的细胞，并且与风湿性关节炎的疾病活动有关。我们的文化系统在体外生产的骨破坏过程中，包括预cursor细胞、极化、激活和骨组织还原的增殖和融合。This system may provide a tool for understanding the mechanisms of bone destruction in rheumatoid arthritis and for the development of new therapies to prevent bone destruction。

Osteoclasts, bone resorbing cells in human tissues, may be involved in the process of rheumatoid bone destruction. To test this hypothesis, we developed an in vitro model of bone destruction by osteoclast-like cells derived from cultured rheumatoid synovial tissue without using any inducers. When a piece of rheumatoid synovial tissue was cultured on the plate, fibroblast- and macrophage-like cells came out from the tissue and proliferated in the coexistence of lymphocytes. After 14 days of culture, multinucleated cells with tartrate-resistant acid phosphatase activity appeared. These cells expressed vacuolar HィイD1+ィエD1-ATPase, the vitronectin receptor, and cathepsin K. Although [ィイD1125|ィエD1]-salmon calcitonin binding was very low, the cells contained ringed structures of F-actin and showed strong bone resorbing activity on ivory slices. Proliferation of macrophage-like cells and formation of multinucleated cells continued during 6 months of culture in the presence of fibroblast-like cells. The bone-resorbing activity of multinucleated cells derived from rheumatoid synovial tissue was much higher than that of cells from osteoarthritis synovial tissue, and was related to the disease activity of rheumatoid arthritis. Our culture system reproduced in vitro the process of bone destruction by rheumatoid synovium, including the proliferation and fusion of precursor cells, polarization, activation, and bone tissue resorption. This system may provide a tool for understanding the mechanisms of bone destruction in rheumatoid arthritis and for the development of new therapies to prevent bone destruction.