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 journalArticle

14 Citations (Scopus)

Abstract

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
JournalAmerican Journal of Physiology - Cell Physiology
Volume293
Issue number4
DOIs
Publication statusPublished - 2007 Oct

Fingerprint

Bone Development
Cartilage
Extracellular Matrix
Bone
Collagen Type II
Embryonic Structures
Proteolysis
Chondrocytes
Growth
Collagen Type X
Growth Plate
DNA Nucleotidylexotransferase
Collagenases
Bromodeoxyuridine
Fibronectins
Integrins
Degradation
Matrix Metalloproteinase 1
Transgenic Mice
Embryonic Development

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Imai, K., Dalal, S. S., Hambor, J., Mitchell, P., Okada, Y., Horton, W. C., & D'Armiento, J. (2007). Bone growth retardation in mouse embryos expressing human collagenase 1. American Journal of Physiology - Cell Physiology, 293(4). https://doi.org/10.1152/ajpcell.00213.2007

Bone growth retardation in mouse embryos expressing human collagenase 1. / Imai, Kazushi; Dalal, Seema S.; Hambor, John; Mitchell, Peter; Okada, Yasunori; Horton, William C.; D'Armiento, Jeanine.

In: American Journal of Physiology - Cell Physiology, Vol. 293, No. 4, 10.2007.

Research output: Contribution to journalArticle

Imai, K, Dalal, SS, Hambor, J, Mitchell, P, Okada, Y, Horton, WC & D'Armiento, J 2007, 'Bone growth retardation in mouse embryos expressing human collagenase 1', American Journal of Physiology - Cell Physiology, vol. 293, no. 4. https://doi.org/10.1152/ajpcell.00213.2007
Imai, Kazushi ; Dalal, Seema S. ; Hambor, John ; Mitchell, Peter ; Okada, Yasunori ; Horton, William C. ; D'Armiento, Jeanine. / Bone growth retardation in mouse embryos expressing human collagenase 1. In: American Journal of Physiology - Cell Physiology. 2007 ; Vol. 293, No. 4.
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