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Design of a Biaxial Mechanical Loading Bioreactor for Tissue Engineering
Published on: April 25, 2013
AP-1 DNA binding activity regulates the cartilage tissue remodeling process following cyclic compression in vitro
J N A De Croos1, R M Pilliar, R A Kandel
1CIHR BioEngineering of Skeletal Tissues Team, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
Biorheology
|October 7, 2008
Summary
Cyclic compression enhances bioengineered cartilage by increasing matrix proteins. This process involves matrix metalloproteinases (MMPs) regulated by AP-1 DNA binding, crucial for cartilage remodeling.
Area of Science:
- Biomaterials Engineering
- Tissue Engineering
- Cellular Mechanobiology
Background:
- Bioengineered cartilage often exhibits inferior physical properties compared to native tissue.
- Cyclic compression of chondrocytes on calcium polyphosphate substrates enhances matrix accumulation.
- The precise mechanism behind this enhancement, particularly the role of matrix remodeling, requires further elucidation.
Purpose of the Study:
- To investigate the role of activating protein-1 (AP-1) in the mechano-induction of matrix metalloproteinases (MMPs) during cartilage tissue engineering.
- To determine if inhibiting AP-1 DNA binding affects MMP transcription and subsequent matrix accumulation.
- To elucidate the mechanism by which cyclic compression enhances cartilage matrix formation.
Main Methods:
- Chondrocytes seeded on calcium polyphosphate substrates were subjected to cyclic compression.
- Modified decoy oligodeoxynucleotides (ODNs) targeting AP-1 DNA binding sites were used.
- Electrophoretic mobility shift assays (EMSAs) were employed to detect AP-1 DNA binding.
- Quantitative analysis of matrix component accumulation (collagens and proteoglycans) and MMP gene transcription was performed.
Main Results:
- Cyclic compression significantly increased collagen and proteoglycan accumulation within 24 hours.
- Mechanical stimulation led to increased transcription of MMP-3 and MMP-13.
- Inhibition of AP-1 DNA binding using ODNs blocked MMP-3 and MMP-13 transcription.
- Blocking AP-1 DNA binding also prevented the enhanced accumulation of collagens and proteoglycans.
Conclusions:
- Mechano-induction of MMP-3 and MMP-13 in cartilage cells is regulated at the AP-1 DNA binding site.
- Upregulation of MMP-3 and MMP-13 is a necessary component of the matrix remodeling process initiated by cyclic compression.
- Targeting the AP-1 pathway offers a potential strategy to control matrix remodeling in cartilage tissue engineering.
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