Bone growth retardation in mouse embryos expressing human collagenase 1

Kazushi Imai, Seema S. Dalal, John Hambor, Peter Mitchell, Yasunori Okada, William C. Horton, Jeanine D'Armiento

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


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 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.

Original languageEnglish
Pages (from-to)C1209-C1215
JournalAmerican Journal of Physiology - Cell Physiology
Issue number4
Publication statusPublished - 2007 Oct


  • Chondrocyte
  • Fibronectin
  • Integrin
  • Matrix metalloproteinase
  • Type II collagen

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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