Matrix metalloproteinases in the formation of human synovial joint cavities.

Matrix metalloproteinases (MMPs) have been implicated in tissue remodelling in growth and development. A histochemical study of human fetal limbs was undertaken to assess the presence, and consequently the possible role, of MMPs and their inhibitor TIMP-1 (tissue inhibitor of metalloproteinases-1) in synovial joint cavity formation. Cryostat sections of fetal limbs from 7 to 14 wk gestation were stained with specific antibodies to collagenase (MMP-1), gelantinases A (MMP-2) and B (MMP-9), stromelysin (MMP-3) and TIMP-1. Immunoreactive (IR) MMP-1, MMP-2 and MMP-3 were seen chiefly in chondrocytes, but in all cases in zones distant from the joint line before cavity formation. IR-MMP-1 and MMP-2 were also localised both in synovium and on the articular surfaces of joints after cavity formation. In addition IR-MMP-2 was seen in a "collar' of perichondrium alongside the hypertrophic zone of chondrocytes and weakly in bone marrow spaces. IR-MMP-9 was seen in neutrophil leucocytes and in bone marrow spaces. IR-TIMP-1 was generally distributed in connective tissue cells. No IR-MMP (1, 2,3 or 9) was seen along potential joint lines before or at the time of cavity formation, nor was there aspecific decrease in IR-TIMP-1 at this site. These findings confirm a role for metalloproteinases in developmental processes such as cartilage remodelling and bone marrow space formation. MMP-1 and MMP-2 may be involved in the remodelling of developing synovial tissue and the articular surfaces subsequent to cavity formation. However, we have failed to find evidence to indicate that the loss of tissue strength at the joint line which allows synovial joint cavity formation relates to high local levels of MMPS.