MATRIX METALLOPROTEINASES AND TIMP-1 LOCALIZATION AT SITES OF OSTEOGENESIS IN THE CRANIOFACIAL REGION OF THE RABBIT EMBRYO

Background: The matrix metalloproteinases (MMPs) are a family of close ly related enzymes, the principal members being the collagenases, gela tinases, and stromelysins. They are synthesized and secreted by connec tive tissue cells and are capable of degrading all the components of c onnective tissue matrices at physiological pH. Methods: Patterns of sy nthesis and distribution of MMPs and their inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1), are documented in the craniofacial region at sites of bone formation during both intramembranous (e.g., c alvaria, maxilla, and mandible) and endochondral ossification (e.g., c artilaginous cranial base and synchondroses) using indirect immunoloca lization. Results: MMPs and TIMP-1 were detected both as bright intrac ellular accumulations, indicating active synthesis, and as diffuse mat rix-bound extracellular deposits. Gelatinase-A had an extensive distri bution in osteogenic tissues and was detected both in cells of the per iosteum and spongiosum and as extracellular deposits in the osteoid la yer of newly formed bone. In addition, gelatinase-AB synthesis was det ected in osteoclasts. All regions of the early cartilaginous cranial b ase produced MMPs and TIMP-1, and synthesis continued in the establish ed synchondrosis. MMPs and TIMP-1 were also documented in early tooth germs and in Meckel's cartilage. Conclusions: These data document a pr ominent role for MMPs, and in particular gelatinase-A, in mediating ma trix degradation during osteogenesis. Their detection in tooth germs a nd Meckel's cartilage further indicates a role for MMPs and TIMP-1 in matrix turnover during morphogenesis. (C) 1995 Wiley-Liss, Inc.