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 closely related enzymes, the principal members being the collagenases, gelatinases, and stromelysins. They are synthesized and secreted by connective tissue cells and are capable of degrading all the components of connective tissue matrices at physiological pH.


METHODS
Patterns of synthesis 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., calvaria, maxilla, and mandible) and endochondral ossification (e.g., cartilaginous cranial base and synchondroses) using indirect immunolocalization.


RESULTS
MMPs and TIMP-1 were detected both as bright intracellular accumulations, indicating active synthesis, and as diffuse matrix-bound extracellular deposits. Gelatinase-A had an extensive distribution in osteogenic tissues and was detected both in cells of the periosteum and spongiosum and as extracellular deposits in the osteoid layer of newly formed bone. In addition, gelatinase-AB synthesis was detected in osteoclasts. All regions of the early cartilaginous cranial base produced MMPs and TIMP-1, and synthesis continued in the established synchondrosis. MMPs and TIMP-1 were also documented in early tooth germs and in Meckel's cartilage.


CONCLUSIONS
These data document a prominent role for MMPs, and in particular gelatinase-A, in mediating matrix degradation during osteogenesis. Their detection in tooth germs and Meckel's cartilage further indicates a role for MMPs and TIMP-1 in matrix turnover during morphogenesis.
Breckon
J J
JJ
Department of Orthodontics and Paediatric Dentistry, Guy's Hospital, London, United Kingdom.
Hembry
R M
RM
Reynolds
J J
JJ
Meikle
M C
MC
D000818:Animals; D017364:Collagenases / Q000378:metabolism; D005147:Facial Bones / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D018093:Gelatinases / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000378:metabolism*; D010012:Osteogenesis; D011247:Pregnancy; D011817:Rabbits; D012886:Skull / Q000196:embryology* / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3