COLLAGENASE-3 (MMP-13) IS EXPRESSED BY HYPERTROPHIC CHONDROCYTES, PERIOSTEAL CELLS, AND OSTEOBLASTS DURING HUMAN FETAL BONE-DEVELOPMENT

Collagenase-3 (MMP-13) is a novel matrix metalloproteinase, the expres sion of which has so far only been documented in human breast carcinom as and osteoarthritic cartilage. In this study we have examined the ex pression of MMP-13 during human fetal development, Northern blot hybri dizations revealed abundant expression of MMP-13 mRNAs in total RNA fr om fetal cartilage and calvaria at gestational age of 15 weeks, By in situ hybridization MMP-13 transcripts were detected in chondrocytes of hypertrophic cartilage in vertebrae of the spinal column and in the d orsal end of ribs undergoing ossification, as well as in osteoblasts a nd periosteal cells below the inner periosteal region of ossified ribs , In contrast, no expression of MMP-13 could be detected in osteoclast s, Furthermore, expression of MMP-13 mRNA was detected in osteoblasts and fibroblasts primarily on the inner side of calvarial bone of the s kull at 16 weeks of gestation, Expression of MMP-13 mRNA by primary hu man fetal chondrocytes in culture was enhanced by transforming growth factor-beta (TGF-beta) and inhibited by bone morphogenetic protein-2 ( BMP-2), No expression of MMP-13 mRNA could be noted in other fetal tis sues, including the skin, lungs, neural tissue, muscle, and liver, The se results suggest that MMP-13 plays an important role in the extracel lular matrix remodeling during fetal bone development both via endocho ndral and intramembranous ossification. (C) 1997 Wiley-Liss, Inc.