EXPRESSION OF 92 KD TYPE-IV COLLAGENASE GELATINASE-B IN HUMAN OSTEOCLASTS

The digestion of type I collagen is an essential step in bone resorpti on. It is well established that osteoclasts solubilize the mineral pha se of bone during the resorptive process, but the mechanism by which t hey degrade type I collagen, the major proteinaceous component of bone , is controversial. Differential screening of a human osteoclastoma cD NA library was performed to characterize genes specifically expressed in osteoclasts. A large number of cDNA clones obtained by this procedu re were found to represent 92 kD type IV collagenase (gelatinase B; MM P-9, EC 3.4.24.35), as well as tartrate-resistant acid phosphatase. In situ hybridization localized mRNA for gelatinase B to multinucleated giant cells in human osteoclastomas. Gelatinase B immunoreactivity was demonstrated in giant cells from eight of eight osteoclastomas, osteo clasts in normal bone, and osteoclasts of Paget's disease by use of a polyclonal antiserum raised against a synthetic gelatinase B peptide. In contrast, no immunoreactivity for 72 kD type IV collagenase (gelati nase A; MMP-2, EC 3.4.24.24), which is the product of a separate gene, was detected in osteoclastomas or normal osteoclasts. We propose that the 92 kD type IV collagenase/gelatinase B plays an important role in the resorption of collagen during bone remodeling.