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. 1997 Jul;191(Pt 1):39–48. doi: 10.1046/j.1469-7580.1997.19110039.x

Distribution of matrix metalloproteinases and their inhibitor, TIMP-1, in developing human osteophytic bone

SHARYN BORD 1 , ALAN HORNER 1 , ROSALIND M HEMBRY 2 , JOHN J REYNOLDS 3 , JULIET E COMPSTON 1
PMCID: PMC1467657  PMID: 9279657

Abstract

Connective tissues synthesise and secrete a family of matrix metalloproteinases (MMPs) which are capable of degrading most components of the extracellular matrix. Animal studies suggest that the MMPs play a role in bone turnover. Using specific polyclonal antisera, immunohistochemistry was used to determine the patterns of synthesis and distribution of collagenase (MMP-1), stromelysin (MMP-3), gelatinase A (MMP-2) and gelatinase B (MMP-9) and of the tissue inhibitor of metalloproteinases-1 (TIMP-1) within developing human osteophytic bone. The different MMPs and TIMP showed distinct patterns of localisation. Collagenase expression was seen at sites of vascular invasion, in osteoblasts synthesising new matrix and in some osteoclasts at sites of resorption. Chondrocytes demonstrated variable levels of collagenase and stromelysin expression throughout the proliferative and hypertrophic regions, stromelysin showing both cell-associated and strong matrix staining. Intense gelatinase B expression was observed at sites of bone resorption in osteoclasts and mononuclear cells. Gelatinase A was only weakly expressed in the fibrocartilage adjacent to areas of endochondral ossification. There was widespread but variable expression of TIMP-1 throughout the fibrous tissue, cartilage and bone. These results indicate that MMPs play a role in the development of human bone from cartilage and fibrous tissue and are likely to have multiple functions.

Keywords: Collagenase, gelatinase, stromelysin, osteoblasts, osteoclasts

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Selected References

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