Induction of CD44 and MMP expression by hyaluronidase treatment of articular chondrocytes
Induction of CD44 and MMP expression by hyaluronidase treatment of articular chondrocytes
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DOI：
10.1093/jb/mvh069
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发表时间：
2004-05-01
影响因子：
2.7
通讯作者：
Tanne, K
中科院分区：
文献类型：
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作者：
Ohno-Nakahara, M;Honda, K;Tanne, K
本研究观察了透明质酸酶(HAase)对关节软骨细胞CD44受体和基质金属蛋白酶(MMP)mRNAs表达的影响。从兔和牛关节软骨分离的软骨细胞，在存在或不存在CD44抗体的情况下，用牛睾丸HAase(0-200单位/毫升)处理。RT-PCR检测CD44、CD44变异体(CD44v)、基质金属蛋白酶(MMPs)、基质金属蛋白酶组织抑制物(TIMP-1、TIMP-2)的mRNA水平。用HAase处理培养的软骨细胞，可产生低相对分子质量的透明质酸(HA)片段。经HAase处理后，CD44、CD44v和基质金属蛋白酶-1、-3、-9的mRNAs表达上调，而TIMP-1和TIMP-2mRNAs的表达不受HAase的影响，而1.0×10(5)Da的纯化HA对其表达无明显影响。此外，抗CD44抗体可抑制HAase对CD44和MMPs的诱导。提示透明质酸碎裂可能通过上调MMPs的表达和上调CD44的表达而导致软骨的破坏。
In this study, the effects of fragmentation of the glycosoaminoglycans of the cell-associated matrix by hyaluronidase (HAase) on the expression of CD44 receptor and matrix metalloproteinase (MMP) mRNAs in cultured articular chondrocytes were examined. Chondrocytes, isolated from rabbit and bovine articular cartilage, were treated with bovine testicular HAase (0-200 units/ml) in the presence or absence of an antibody for CD44. The mRNA levels of CD44, CD44 variant (CD44v), MMPs (MMP-1, 3 and -9), and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were determined by RT-PCR. The treatment of cultured chondrocytes with HAase resulted in the production of low molecular weight fragments of hyaluronan (HA). The expression of CD44, CD44v and MMP (MMP-1, -3 and -9) mRNAs, but not TIMP-1 or TIMP-2 mRNA, was up-regulated in the cultures treated with HAase, whereas this expression was not affected by treatment with purified HA of 1.0 x 10(5) Da. Furthermore, the induction of CD44 and MMPs on treatment with HAase was suppressed by an anti-CD44 antibody. The results suggest that the fragmentation of HA may lead to cartilage destruction in terms of the enhanced expression of MMPs as well as the upregulation of CD44.