聚蛋白多糖酶
阿达姆斯
阿格里坎
去整合素
化学
金属蛋白酶
基质金属蛋白酶
血栓反应素
抗体
分子生物学
细胞生物学
骨关节炎
免疫学
生物
生物化学
医学
病理
关节软骨
替代医学
作者
Aya Shiraishi,Satsuki Mochizuki,Akira Miyakoshi,Kanehisa Kojoh,Yasunori Okada
标识
DOI:10.1016/j.bbrc.2015.11.072
摘要
ADAMTS4 (aggrecanase-1) and ADAMTS5 (aggrecanase-2), members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family, are considered to play a key role in aggrecan degradation of articular cartilage in human osteoarthritis. Here, we developed a neutralizing antibody to these aggrecanases by screening human combinatorial antibody library. Among the five candidate antibodies, one antibody was immunoreactive with both ADAMTS4 and ADAMTS5, showing no or negligible cross-reactivity with 10 different related metalloproteinases of the ADAMTS, ADAM (a disintegrin and metalloproteinase) and MMP (matrix metalloproteinase) gene families. This antibody almost completely and partially inhibited aggrecanase activity of ADAMTS4 and ADAMTS5, respectively. It also suppressed the aggrecanase activity derived from interleukin-1-stimulated osteoarthritic chondrocytes. These data demonstrate that the antibody is specific to ADAMTS4 and ADAMTS5 and inhibits their aggrecanase activity at molecular and cellular levels, and suggest that this antibody may be useful for treatment of pathological conditions such as osteoarthritis.
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