Wucherpfennig A L, Li Y P, Stetler-Stevenson W G, Rosenberg A E, Stashenko P
Department of Cytokine Biology, Forsyth Research Institute, Boston, Massachusetts.
J Bone Miner Res. 1994 Apr;9(4):549-56. doi: 10.1002/jbmr.5650090415.
The digestion of type I collagen is an essential step in bone resorption. It is well established that osteoclasts solubilize the mineral phase of bone during the resorptive process, but the mechanism by which they degrade type I collagen, the major proteinaceous component of bone, is controversial. Differential screening of a human osteoclastoma cDNA library was performed to characterize genes specifically expressed in osteoclasts. A large number of cDNA clones obtained by this procedure were found to represent 92 kD type IV collagenase (gelatinase B; MMP-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, osteoclasts 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 (gelatinase 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.
I型胶原的消化是骨吸收的关键步骤。众所周知，破骨细胞在吸收过程中溶解骨的矿质相，但它们降解骨的主要蛋白质成分I型胶原的机制仍存在争议。通过差异筛选人破骨细胞瘤cDNA文库来鉴定破骨细胞中特异性表达的基因。通过该方法获得的大量cDNA克隆被发现代表92kD IV型胶原酶（明胶酶B；MMP-9，EC 3.4.24.35）以及抗酒石酸酸性磷酸酶。原位杂交将明胶酶B的mRNA定位于人破骨细胞瘤中的多核巨细胞。通过使用针对合成明胶酶B肽产生的多克隆抗血清，在8个破骨细胞瘤中的8个的巨细胞、正常骨中的破骨细胞以及佩吉特病的破骨细胞中均证实了明胶酶B免疫反应性。相比之下，在破骨细胞瘤或正常破骨细胞中未检测到72kD IV型胶原酶（明胶酶A；MMP-2，EC 3.4.24.24）的免疫反应性，72kD IV型胶原酶是另一个基因的产物。我们认为92kD IV型胶原酶/明胶酶B在骨重塑过程中胶原的吸收中起重要作用。
