To explore possible physiologic functions for the
metalloproteinase collagenase-3, we have examined its temporal and spatial expression during human fetal development. Except for mesenchymal cells in the umbilical cord at 4 weeks of gestation, signal for
collagenase-3 mRNA was confined to mineralizing skeletal tissue and detected in hypertrophic chondrocytes and osteoblastic cells involved in ossification beginning
at 10 weeks and continuing through gestation. These cells were also immunoreactive with
collagenase-3 antiserum, indicating their ability to produce
collagenase-3 protein. In osteoblastic cells, the expression of membrane-type 1
metalloproteinase and 72-kd
gelatinase mRNA, which have the capacity to activate
collagenase-3 in vitro, colocalized with that of
collagenase-3. In postnatal tissues,
collagenase-3 was re-expressed in processes involving skeletal remodeling, such as
bone cysts and ectopic bone and cartilage formation. Multinucleated osteoclasts were consistently negative for
collagenase-3. Furthermore, in patients with seropositive
rheumatoid arthritis, expression of
collagenase-3 was prominent in articular cartilage, and
collagenase-3 protein was detected by immunoblotting in synovial fluids. Consistent with its substrate specificities, a plausible function for
collagenase-3 in these processes is to preferentially degrade
type II collagen, thus serving a role during primary ossification, in skeletal remodeling, and in destructive
joint disease.