(PRO)COLLAGENASE (MATRIX METALLOPROTEINASE-1) IS PRESENT IN RODENT OSTEOCLASTS AND IN THE UNDERLYING BONE-RESORBING COMPARTMENT

Osteoclasts resorb the extracellular matrix of bone by secreting enzym es and acid into a sealed-off compartment that they form upon attachme nt to the bone surface. Although the lysosomal cysteine proteinases ca n degrade collagen after the demineralization of bone at low pH, sever al lines of evidence suggest that collagenase (matrix metalloproteinas e-1, EC 3.4.24.7) may also be involved in this process. The question o f whether collagenase is present in the osteoclast and/or in the bone- resorbing compartment has however not been resolved. We have prepared an anti-mouse collagenase antiserum and affinity-purified an IgG fract ion that specifically immunoblots and immunoprecipitates (pro)collagen ase. Using these antibodies, we demonstrate by immunolocalization the presence of (pro)collagenase both in the osteoclasts and in the extrac ellular subosteoclastic bone-resorbing compartment. These specific loc alizations were observed not only in mice but also in rat and rabbit o steoclasts and using not only the antibody we have prepared but also a ntibodies raised in other laboratories against rat (Jeffrey et al., J. Cell. Physiol. 143, 396-403, 1990) and rabbit (Brinckerhoff et al., J . Biol. Chem. 265, 22262-22269, 1990) collagenase. Intracellular colla genase was observed in the osteoclasts whether the cells were plated o n bone or cultured on glass coverslips. It is proposed that osteoclast ic collagenase is secreted in the resorbing compartment where it may c ooperate with the lysosomal cysteine proteinases in the degradation of the collagen component of the matrix during the resorption of bone.