Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage
Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage
复制标题
DOI：
10.1172/jci119316
复制
发表时间：
1997-04-01
影响因子：
15.9
通讯作者：
Poole, AR
中科院分区：
文献类型：
--
作者：
Billinghurst, RC;Dahlberg, L;Poole, AR
我们通过开发和使用针对羧基末端(COL2-3/4C(简称COL2-3/4C)和氨基末端(COL2-1/4N1)的抗体的抗体，证明胶原酶活性的增加直接参与了骨关节炎股骨髁软骨中II型胶原的裂解。胶原酶通常由胶原酶基质金属蛋白酶(MMP1)-1(胶原酶-1)、MMP8(胶原酶-2)和MMP13(胶原酶-3)裂解而成。在这些重组胶原酶产生的初始切割之后发生了二次切割。这产生了新的表位COL2-1/4N2。通过软骨提取液的免疫分析，骨性关节炎(OA)患者的COL2-3/4C(短)新表位显著多于成人非关节炎软骨。人工合成的基质金属蛋白酶-13选择性抑制剂显著减少了培养上清中人骨关节炎软骨新表位COL2-3/4C(Short)的非刺激性释放。这些数据表明，软骨细胞产生的胶原酶(S)参与了关节软骨中II型胶原的裂解和变性，在骨关节炎中这种作用增加，基质金属蛋白酶-13可能在这一过程中发挥重要作用。
We demonstrate the direct involvement of increased collagenase activity in the cleavage of type II collagen in osteoarthritic human femoral condylar cartilage by developing and using antibodies reactive to carboxy-terminal (COL2-3/4C(short)) and amino-terminal (COL2-1/4N1) neoepitopes general ed by cleavage of native human type II collagen by collagenase matrix metalloproteinase (MMP)-1 (collagenase-1), MMP-8 (collagenase-2), and MMP-13 (collagenase-3). A secondary cleavage followed the initial cleavage produced by these recombinant collagenases. This generated neoepitope COL2-1/4N2. There was significantly more COL2-3/4C(short) neoepitope in osteoarthritis (OA) compared to adult nonarthritic cartilages as determined by immunoassay of cartilage extracts. A synthetic preferential inhibitor of MMP-13 significantly reduced the unstimulated release in culture of neoepitope COL2-3/4C(short) from human osteoarthritic cartilage explants. These data suggest that collagenase(s) produced by chondrocytes is (are) involved in the cleavage and denaturation of type II collagen in articular cartilage, that this is increased in OA, and that MMP-13 may play a significant role in this process.