Recombinant matrix metalloproteinase-14 catalytic domain induces apoptosis in human osteoblastic SaOS-2 cells

J Endocrinol Invest. 2003 Nov;26(11):1111-6. doi: 10.1007/BF03345259.

Abstract

Our study previously showed that estrogen and progesterone stimulated the production of matrix metalloproteinase-14 [MMP-14, or also named membrane type matrix metalloproteinses-1 (MT1-MMP)] in osteoblastic cells. MMP-14 was implied to regulate the function of osteoblasts by degrading bone matrix or growth factors, but the mechanism is unclear. Since MMP-14 plays a role primarily through the catalytic domain, and truncated MMP-14 containing the catalytic domain and lacking transmembrane domain can be secreted into medium by cultured cells, our present study was performed to observe the direct effects of recombinant MMP-14 catalytic domain on cultured human osteoblastic osteogenic sarcoma (SaOS)-2 cells. Our data showed that recombinant MMP-14 catalytic domain activated proMMP-2 secreted into media by SaOS-2 cells, and this process was blocked by ethylenediamine tetraacetic acid (EDTA) treatment. Recombinant MMP-14 catalytic domain inhibited the adhesion of SaOS-2 cells to immobilized type I collagen or fibronectin in a dose-dependent manner, and these effects on SaOS-2 cells were abolished by EDTA. Recombinant MMP-14 catalytic domain induced SaOS-2 cells apoptosis in a dose-dependent manner, and apoptosis-inducing activity of MMP-14 catalytic domain was blocked if it was treated with EDTA. In conclusion, we revealed that recombinant MMP-14 catalytic domain induced SaOS-2 cells apoptosis. We also indirectly showed the activity of MMP-14 catalytic domain to degrade extracellular matrix (ECM) in cultures of SaOS-2 cells through Gelatin Zymograms and adhesion assay. This suggests that since adhesion of cells to ECM serves as a survival mechanism in osteoblasts, the catalytic activity of recombinant MMP-14 catalytic domain on matrix proteins contributes to its apoptosis-inducing activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Blotting, Western
  • Catalytic Domain
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Line, Tumor
  • Edetic Acid / pharmacology
  • Humans
  • Immunoenzyme Techniques
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / antagonists & inhibitors
  • Metalloendopeptidases / metabolism
  • Metalloendopeptidases / pharmacology*
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / enzymology
  • Osteoblasts / metabolism
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • Recombinant Proteins
  • Edetic Acid
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases