Related Experiment Video
Updated: Jul 10, 2026
Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells
Published on: June 13, 2018
Recombinant matrix metalloproteinase-14 catalytic domain induces apoptosis in human osteoblastic SaOS-2 cells
1Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China. xianghangluo@21cn.com
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.
Insights
The catalytic domain of matrix metalloproteinase-14 (MMP-14) directly induces apoptosis in osteoblastic SaOS-2 cells. This MMP-14 activity also degrades extracellular matrix, impairing cell adhesion and survival.
Area of Science:
- Biochemistry
- Cell Biology
- Bone Biology
Background:
- Estrogen and progesterone stimulate matrix metalloproteinase-14 (MMP-14) production in osteoblasts.
- MMP-14's role in osteoblast function via matrix degradation is unclear.
- The catalytic domain of MMP-14 is crucial for its function.
Purpose of the Study:
- To investigate the direct effects of the recombinant MMP-14 catalytic domain on human osteoblastic SaOS-2 cells.
- To elucidate the mechanism by which MMP-14 influences osteoblast behavior.
Main Methods:
- Treatment of SaOS-2 cells with recombinant MMP-14 catalytic domain.
- Assessing proMMP-2 activation using EDTA as a control.
- Evaluating SaOS-2 cell adhesion to collagen and fibronectin.
- Inducing and quantifying SaOS-2 cell apoptosis.
- Utilizing Gelatin Zymograms and adhesion assays.
Main Results:
- Recombinant MMP-14 catalytic domain activated proMMP-2, an effect inhibited by EDTA.
- MMP-14 catalytic domain dose-dependently inhibited SaOS-2 cell adhesion to collagen and fibronectin, blocked by EDTA.
- Recombinant MMP-14 catalytic domain induced SaOS-2 cell apoptosis in a dose-dependent manner, with activity blocked by EDTA.
- Degradation of extracellular matrix by MMP-14 catalytic domain was confirmed.
Conclusions:
- The MMP-14 catalytic domain induces apoptosis in osteoblastic SaOS-2 cells.
- MMP-14 catalytic activity on extracellular matrix proteins contributes to its apoptosis-inducing effects.
- Impaired cell adhesion to the ECM, a survival mechanism, likely mediates MMP-14-induced apoptosis.
