椎間板ヘルニア退縮機序で作用するMMP

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MRI study has shown that epidurally displaced herniated disc (HD) tissues more commonly exhibited a gradual decrease in the size of HD than those with minimal protrusion. Surgical samples from HD show granulation tissue with prominent macrophage and mild T-lymphocyte infiltration concomitant with the onset of neovascularization that is not observed in healthy intervertebral disc, Changes initiated by contact with infiltrating macrophages may thus contribute to the resoprption process. We've then developed a coculture system of disc tissues and macrophages to reproduce the acute phase of disc herniation in vitro. We've determined that infiltrated macrophages and disc cells in HD tissues express the matrix metalloproteinases (MMPs) MMP-3 and MMP-7, both of which are potent proteglycanases. MMP-3 and MMP-7 are strongly upregulated when macrophages are added to disc tissues in our coculture model. The interesting observation from our current study is the role of chondrocyte MMP-3 in the generation of a chemotactic factor that induces macrophage infiltration. MMP-3-null discs did not allow macrophage infiltration in the organ coculture model, and isolated chondrocytes lacking MMP-3 did not allow macrophage infiltration of alginate beads. In addition, coculture medium from wild type macrophages and MMP-3-null discs did not produce macrophage chemoattractants in the checkerboard chemoattraction assay. The nature of the MMP-3-dependent chemoattractant is not clear. MMP-3 mediated degradation of matrix components may release macrophage chemoattractants. Irrespective of the molecular nature of the chemoattractant, this is to our knowledge the first example of a definitive role for MMP-3 in a chemoattractive process.
日本結合組織学会の論文
2001-03-25

椎間板ヘルニア退縮機序で作用するMMP

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