Journal
JOURNAL OF RHEUMATOLOGY
Volume 38, Issue 5, Pages 911-920Publisher
J RHEUMATOL PUBL CO
DOI: 10.3899/jrheum.100710
Keywords
PROTEINASE-ACTIVATED RECEPTOR-2; OSTEOARTHRITIS; MOUSE; CARTILAGE; SUBCHONDRAL BONE
Categories
Funding
- Canadian Institutes of Health Research (CIHR) [MOP-86478]
- Fonds de la Recherche en Sante du Quebec
- MENTOR/CIHR
Ask authors/readers for more resources
Objective. Evidence indicates that proteinase-activated receptor (PAR)-2 participates in the degradative processes of human osteoarthritis (OA). We evaluated the in viva effect of PAR-2 on articular lesions in a PAR-2-knockout (KO) mouse model of OA. Methods. OA was surgically induced by destabilization of the medial meniscus of the right knee in C57B1/6 wild-type (WT) and PAR-2 KO mice. Knee swelling was measured throughout the duration of the study (8 weeks postsurgery) and histologic evaluation of cartilage was done to assess structure, cellularity, matrix staining, and remodeling in the deep zone. Morphometric analysis of subchondral bone was also performed. Results. Data showed significant knee swelling in the operated WT mice immediately following surgery, which increased with time (8 weeks post-surgery). Knee swelling was significantly lower (p <= 0.0001) in PAR-2 KO mice than in WT mice at both 4 and 8 weeks postsurgery. Cartilage damage was found in both operated WT and PAR-2 KO mice; however, lesions were significantly less severe (global score; p <= 0.05) in the PAR-2 KO mice at 4 weeks postsurgery. Operated WT mice showed reduced subchondral bone surface and trabecular thickness with significance reached at 4 weeks (p <= 0.03 and p <= 0.05, respectively), while PAR-2 KO mice demonstrated a gradual increase in subchondral bone surface with significance reached at 8 weeks (p <= 0.007). Conclusion. We demonstrated the in viva implication of PAR-2 in the development of experimental OA, thus confirming its involvement in OA joint structural changes and reinforcing the therapeutic potential of a PAR-2 antagonist for treatment of OA. (First Release Feb 1 2011; J Rheumatol 2011;38:911-20; doi:10.3899/jrheum.100710)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available