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 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.
Vu
T H
TH
Department of Anatomy, University of California, San Francisco 94143, USA.
Shipley
J M
JM
Bergers
G
G
Berger
J E
JE
Helms
J A
JA
Hanahan
D
D
Shapiro
S D
SD
Senior
R M
RM
Werb
Z
Z
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002356:Cartilage / Q000098:blood supply / Q000473:pathology; D002417:Cattle; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology*; D003094:Collagen; D017364:Collagenases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000166:cytology; D005782:Gels; D006132:Growth Plate / Q000002:abnormalities / Q000098:blood supply* / Q000737:chemistry / Q000254:growth & development; D006984:Hypertrophy; D020780:Matrix Metalloproteinase 9; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010012:Osteogenesis / Q000502:physiology
D005782:Gels; D003094:Collagen; D017364:Collagenases; D020780:Matrix Metalloproteinase 9