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
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
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
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.