MMP-9/Gelatinase B Is a Key Regulator of Growth Plate Angiogenesis and Apoptosis of Hypertrophic Chondrocytes

Homozygous mice with a null mutation in the MMP-9/gelatinase B gene exhibit an abnormal pattern of skeletal growth plate vascularization and ossification. Although hypertrophic chondrocytes develop normally, apoptosis, vascularization, and ossification are delayed, resulting in progressive lengtheni...

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Bibliographic Details
Published in:Cell 1998-05, Vol.93 (3), p.411-422
Main Authors: Vu, Thiennu H, Shipley, J.Michael, Bergers, Gabriele, Berger, Joel E, Helms, Jill A, Hanahan, Douglas, Shapiro, Steven D, Senior, Robert M, Werb, Zena
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Bone Marrow Transplantation
Cartilage - blood supply
Cartilage - pathology
Cattle
Cell Differentiation
Chondrocytes - cytology
Collagen
Collagenases - analysis
Collagenases - genetics
Collagenases - physiology
Culture Techniques
Endothelium, Vascular - cytology
Gels
Growth Plate - abnormalities
Growth Plate - blood supply
Growth Plate - chemistry
Growth Plate - growth & development
Hypertrophy
Matrix Metalloproteinase 9
Mice
Mice, Knockout
Neovascularization, Physiologic - genetics
Osteogenesis - physiology
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Summary:Homozygous mice with a null mutation in the MMP-9/gelatinase B gene exhibit an abnormal pattern of skeletal growth plate vascularization and ossification. Although hypertrophic chondrocytes develop normally, apoptosis, vascularization, and ossification are delayed, resulting in progressive lengthening of the growth plate to about eight times normal. After 3 weeks postnatal, aberrant apoptosis, vascularization, and ossification compensate to remodel the enlarged growth plate and ultimately produce an axial skeleton of normal appearance. Transplantation of wild-type bone marrow cells rescues vascularization and ossification in gelatinase B–null growth plates, indicating that these processes are mediated by gelatinase B–expressing cells of bone marrow origin, designated chondroclasts. Growth plates from gelatinase B–null mice in culture show a delayed release of an angiogenic activator, establishing a role for this proteinase in controlling angiogenesis.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)81169-1