| First Author | Imai K | Year | 2007 |
| Journal | Am J Physiol Cell Physiol | Volume | 293 |
| Issue | 4 | Pages | C1209-15 |
| PubMed ID | 17652426 | Mgi Jnum | J:128720 |
| Mgi Id | MGI:3767906 | Doi | 10.1152/ajpcell.00213.2007 |
| Citation | Imai K, et al. (2007) Bone growth retardation in mouse embryos expressing human collagenase 1. Am J Physiol Cell Physiol 293(4):C1209-15 |
| abstractText | 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. |
