MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes

被引:1489
作者
Vu, TH
Shipley, JM
Bergers, G
Berger, JE
Helms, JA
Hanahan, D
Shapiro, SD
Senior, RM
Werb, Z
机构
[1] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Med, Dept Orthoped Surg, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Dept Med, Hormone Res Inst, San Francisco, CA 94143 USA
[5] Washington Univ, Sch Med, Barnes Jewish Hosp, Dept Internal Med,Div Pulm & Crit Care Med, St Louis, MO 63110 USA
[6] Washington Univ, Sch Med, Barnes Jewish Hosp, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
关键词
D O I
10.1016/S0092-8674(00)81169-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:411 / 422
页数:12
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