Lauren B Manning
Harard School of Dental Medicine, USA
Posters & Accepted Abstracts: J Bioengineer & Biomedical Sci
Introduction: Currently, no targets for disease-modifying osteoarthritis drugs exist. Co-localized expression of discoidin domain receptor 2 (DDR2) and matrix metalloproteinase 13 (MMP-13) has been found in degenerative articular cartilage of both human OA tissues and mouse models of OA. In healthy articular cartilage, DDR2 is kept inactivated by the peri-cellular matrix; however, once lost, DDR2 is activated and induces expression of MMP-13, resulting in joint destruction and OA. Methods: We generated aggrecan-CreERt2 mice and floxed Ddr2 mice and used conditional knock out techniques to remove Ddr2 from articular cartilage of knee joints in 8 week old mice via intra-peritoneal Tamoxifen injection (Group A). Destabilization of the medial meniscus (DMM) or sham surgery was performed at 10 weeks of age. Group B mice were subjected to DMM or sham surgery at 10 weeks of age, followed by DDR2 removal 8 weeks later. Knee joints from mice in Group A were harvested at 8 weeks or 16 weeks post-surgery and from Group B at 16 weeks post-surgery. Histology was performed and the OARSI Modified Mankin Score was used to evaluate articular cartilage degeneration. Statistically significant differences were determined via T-test. Results: The average modified scores were as follows: Group A 8 week control, 1.64 (n=7); Group A 8 week experimental, 0.64 (n=7) [P<0.05]; Group A 16 week control, 4.67 (n=7); Group A 16 week experimental, 1.27 (n=9) [P<0.05]; Group B, 1.1 (n=5). Conclusion: In conclusion, conditional removal of Ddr2 in articular cartilage attenuated articular cartilage degeneration in mature knee joints of mouse models of OA.
Email: manningl@ohsu.edu
Journal of Bioengineering & Biomedical Science received 307 citations as per Google Scholar report
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