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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.

Pubmed ID: 9590175


  • Vu TH
  • Shipley JM
  • Bergers G
  • Berger JE
  • Helms JA
  • Hanahan D
  • Shapiro SD
  • Senior RM
  • Werb Z



Publication Data

May 1, 1998

Associated Grants

  • Agency: NIDCR NIH HHS, Id: DE10306
  • Agency: NICHD NIH HHS, Id: HD26732
  • Agency: NHLBI NIH HHS, Id: HL47328
  • Agency: NICHD NIH HHS, Id: P01 HD026732
  • Agency: NICHD NIH HHS, Id: P01 HD026732-070003
  • Agency: NIDCR NIH HHS, Id: P50 DE010306
  • Agency: NIDCR NIH HHS, Id: P50 DE010306-05S10005
  • Agency: NCI NIH HHS, Id: R01 CA037395-19
  • Agency: NHLBI NIH HHS, Id: R01 HL047328-08
  • Agency: NHLBI NIH HHS, Id: T32 HL007185-26

Mesh Terms

  • Animals
  • Apoptosis
  • Bone Marrow Transplantation
  • Cartilage
  • Cattle
  • Cell Differentiation
  • Chondrocytes
  • Collagen
  • Collagenases
  • Culture Techniques
  • Endothelium, Vascular
  • Gels
  • Growth Plate
  • Hypertrophy
  • Matrix Metalloproteinase 9
  • Mice
  • Mice, Knockout
  • Neovascularization, Physiologic
  • Osteogenesis