Bone growth retardation in mouse embryos expressing human collagenase 1
Bone growth retardation in mouse embryos expressing human collagenase 1
复制标题
DOI：
10.1152/ajpcell.00213.2007
复制
发表时间：
2007-10-01
影响因子：
5.5
通讯作者：
D'Armiento, Jeanine
中科院分区：
文献类型：
--
作者：
Imai, Kazushi;Dalal, Seema S.;D'Armiento, Jeanine
细胞生长和分化是细胞内和/或细胞外环境中多种信号通路的读数。细胞外基质通过激活细胞受体来传递这些信号。因此，细胞外基质蛋白的降解可以在多种生物事件中影响细胞的命运。然而，体内细胞外基质降解不足的生物学后果尚不清楚。我们建立了在Col2a1启动子控制下表达人胶原酶(基质金属蛋白酶-1，MMP1)的小鼠模型。小鼠在胚胎发育过程中表现出明显的生长迟缓，软骨的带状结构和柱状排列的界限消失。免疫学检查显示，转基因软骨中II型胶原降解增加，纤维连接蛋白和α(5)整合素亚单位表达上调。在生长板软骨的静止区和增殖区，溴脱氧尿苷(BrdU)掺入的增殖细胞和末端脱氧核苷酸转移酶介导的X-dUTP缺口末端标记阳性的凋亡细胞分别同时增加。IHH和X型胶原的正常表达表明，转基因小鼠的软骨细胞分化没有受到干扰。这些数据表明，II型胶原蛋白分解通过调节软骨细胞的存活和软骨的生长，是骨骼生长的重要决定因素。
Cellular growth and differentiation are readouts of multiple signaling pathways from the intercellular and/or extracellular milieu. The extracellular matrix through the activation of cellular receptors transmits these signals. Therefore, extracellular matrix proteolysis could affect cell fate in a variety of biological events. However, the biological consequence of inadequate extracellular matrix degradation in vivo is not clear. We developed a mouse model expressing human collagenase ( matrix metalloproteinase-1, MMP-1) under the control of Col2a1 promoter. The mice showed significant growth retardation during embryogenesis and a loss of the demarcation of zonal structure and columnar array of the cartilage. Immunological examination revealed increased degradation of type II collagen and upregulation of fibronectin and alpha(5)-integrin subunit in the transgenic cartilage. The resting zone and proliferating zone of the growth plate cartilage exhibited a simultaneous increase in bromodeoxyuridine ( BrdU)incorporated proliferating cells and terminal deoxynucleotidyl transferase-mediated X-dUTP nick-end labeling-positive apoptotic cells, respectively. Chondrocyte differentiation was not disturbed in the transgenic mice as evidenced by normal expression of the Ihh and type X collagen expression. These data demonstrate that type II collagen proteolysis is an important determinant for the skeletal outgrowth through modulation of chondrocyte survival and cartilagenous growth.