Matrix metalloproteinase-3-dependent generation of a macrophage chemoattractant in a model of herniated disc resorption
Matrix metalloproteinase-3-dependent generation of a macrophage chemoattractant in a model of herniated disc resorption
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DOI：
10.1172/jci7090
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发表时间：
2000-01-01
影响因子：
15.9
通讯作者：
Matrisian, LM
中科院分区：
文献类型：
--
作者：
Haro, H;Crawford, HC;Matrisian, LM
椎间盘突出（HD）是一种常见的健康问题，除非发生自发再吸收，否则可通过手术解决。HD组织含有大量巨噬细胞浸润和高水平的基质金属蛋白酶（MMPs） MMP-3和MMP-7。我们建立了一个模型系统，将野生型或无mmp小鼠的椎间盘组织或分离的软骨细胞与腹膜巨噬细胞共培养，并利用该系统研究MMPs和软骨细胞/巨噬细胞相互作用在椎间盘吸收中的作用。我们观察到暴露于巨噬细胞后软骨细胞中MMP-3蛋白和mRNA的显著增强。通过测定共培养3天后湿重和蛋白多糖含量的减少，可以确定，椎间盘吸收需要软骨细胞MMP-3，而不是MMP-7。令人惊讶的是，巨噬细胞化学吸引剂的产生和随后蛋白水解活性巨噬细胞对椎间盘组织的浸润需要软骨细胞MMP-3。我们得出结论，巨噬细胞诱导软骨细胞MMP-3在椎间盘吸收中起主要作用，其机制包括产生生物活性巨噬细胞化学引诱剂。
Herniated disc (HD) is a common health problem that is resolved by surgery unless spontaneous resorption occurs. HD tissue contains abundant macrophage infiltration and high levels of matrix metalloproteinases (MMPs) MMP-3 and MMP-7. We developed a model system in which disc tissue or isolated chondrocytes from wild-type or MMP-null mice were cocultured with peritoneal macrophages and used this system to investigate the role of MMPs and chondrocyte/macrophage interactions in disc resorption, We observed a marked enhancement of MMP-3 protein and mRNA in chondrocytes after exposure to macrophages. Chondrocytic MMP-3, but not MMP-7, was required for disc resorption, as determined by assaying for a reduction in wet weight and proteoglycan content after 3 days of coculture, Surprisingly, chondrocyte MMP-3 was required for the generation of a macrophage chemoattractant and the subsequent infiltration of the disc tissue by proteolytically active macrophages. We conclude that macrophage induction of chondrocyte MMP-3 plays a major role in disc resorption by mechanisms that include the generation of a bioactive macrophage chemoattractant.