Improved bioengineered cartilage tissue formation following cyclic compression is dependent on upregulation of MT1-MMP.
The generation of bioengineered cartilage tissue suitable for transplantation is a potential therapy to treat damaged cartilage. We have shown previously that the physical and biomechanical properties of bioengineered cartilage can be improved by the application of 30 min of cyclic compression by a mechanism involving sequential upregulation of gene and protein levels of membrane type-1 matrix metalloproteinase (MT1-MMP) and MMP-13. In the current study, we demonstrated that MT1-MMP is critical to this response, as blocking the upregulation of MT1-MMP prevented the improvement in tissue formation. MT1-MMP seems to act by inducing tissue remodeling as evidenced by the presence of aggrecan degradation products by Western blot analysis and increased release of matrix molecules into the media. Release of these molecules was diminished when MT1-MMP upregulation was prevented. This matrix degradation was likely due to MT1-MMP, as under conditions where MMP-13 expression is maintained (stimulation in the presence of MT1-MMP siRNA) the release of these matrix molecules into the media was still prevented. It also appears that MT1-MMP does not regulate MMP-13 gene expression, as MT1-MMP-siRNA pretreatment had no effect on MMP-13 expression following mechanical stimulation. Further analysis of the anabolic genes and proteins involved in mechanically stimulated cartilage will lead to better understanding of the mechanism(s) underlying tissue formation yielding improved bioengineered cartilage.
De Croos
J N Amrith
JN
CIHR BioEngineering of Skeletal Tissues Team, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Suite 6-500, Toronto, Ontario, Canada.
Roughley
Peter J
PJ
Kandel
Rita A
RA
D000818:Animals; D057005:Bioengineering; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D019902:Chondrocytes / Q000502:physiology; D019245:Compressive Strength / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D053511:Matrix Metalloproteinase 14 / Q000235:genetics* / Q000378:metabolism; D008663:Metacarpus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering; D013314:Stress, Mechanical; D015854:Up-Regulation / Q000502:physiology
D034741:RNA, Small Interfering; D053509:Matrix Metalloproteinase 13; D053511:Matrix Metalloproteinase 14