Stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) expression in developing human bone: potential roles in skeletal development.
Stromelysin, a member of the matrix metalloproteinase family, demonstrates wide substrate specificity with the ability to degrade proteoglycan, fibronectin, laminin, casein, and the nonhelical region of collagen. The two forms of stromelysin (SL), types 1 (MMP-3) and 2 (MMP-10), share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. However, the distribution of the two isoforms in bone has not been reported. We investigated the presence of SL-1 and SL-2 in human osteophytic and neonatal rib bone using immunohistochemistry and, combined with a new method of in situ zymography, determined the activity of the immunolocalized stromelysins. Latent SL-1 was strongly expressed in the extracellular matrix in fibrous tissue surrounding areas of endochondral ossification in osteophytes, and adjacent to the periosteum of fetal rib bone. Active SL-1 expression was detected in osteocytes and the matrix surrounding osteocytic lacunae. SL-2 showed intense cell-associated staining at sites of resorption in areas of endochondral ossification and in resorptive cells at the chondro-osseous junction, which correlated with enzyme activity detected by zymography. Within the rib, active SL-2 expression was localized in chondrocytes of the growth plate, whereas only occasional SL-1 signal was evident. Vascular areas showed strong SL-2 staining with some proteolytic activity. SL-2, but not SL-1, was strongly expressed in osteoclasts and most mononuclear cells within the marrow. At sites of bone formation both isoforms were expressed by osteoblasts with SL-1 also present in osteoid. These results demonstrate, for the first time, the differential expression of SL-1 and SL-2 in developing human bone, indicating specific roles for the two isoforms. In situ zymography demonstrates that SL-2 is produced in an active form with associated degradation, whereas SL-1, in a matrix-bound proenzyme form, may act as a reservoir for later activation.
Bord
S
S
Department of Medicine University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, UK. sb201@cam.ac.uk
Horner
A
A
Hembry
R M
RM
Compston
J E
JE
D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D053506:Matrix Metalloproteinase 10; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D009999:Ossification, Heterotopic / Q000201:enzymology* / Q000473:pathology; D010012:Osteogenesis; D012272:Ribs / Q000196:embryology / Q000201:enzymology*
D006023:Glycoproteins; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D053506:Matrix Metalloproteinase 10