MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes
MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes
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DOI：
10.1016/s0092-8674(00)81169-1
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发表时间：
1998-05-01
期刊：
影响因子：
64.5
通讯作者：
Werb, Z
中科院分区：
文献类型：
--
作者：
Vu, TH;Shipley, JM;Werb, Z
MMP-9/明胶酶B基因无效突变的纯合子小鼠表现出骨骼生长板血管化和骨化的异常模式。虽然肥大软骨细胞发育正常，但细胞凋亡、血管形成和骨化延迟，导致生长板逐渐延长至正常的8倍。出生后3周，异常的细胞凋亡、血管化和骨化补偿重塑扩大的生长板，并最终产生外观正常的中轴骨骼。移植野生型骨髓细胞挽救明胶酶B无效生长板中的血管形成和骨化，表明这些过程是由骨髓来源的明胶酶B表达细胞（指定为破软骨细胞）介导的。明胶酶B基因缺失小鼠培养的生长板显示血管生成激活剂的延迟释放，确立了这种蛋白酶在控制血管生成中的作用。
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.