Oral treatment with a Brachystemma calycinum D don plant extract reduces disease symptoms and the development of cartilage lesions in experimental dog osteoarthritis: inhibition of protease-activated receptor 2.
OBJECTIVE
The aims of this study were to evaluate the effect of oral treatment with a whole plant extract of Brachystemma calycinum D don (BCD) on the development of osteoarthritic lesions and symptoms in the experimental dog anterior cruciate ligament (ACL) transection model and to document its mechanism of action.


METHODS
Osteoarthritis was induced by sectioning the ACL of the right knee in crossbred dogs. There were two experimental groups (n=6-7 dogs/group): placebo and BCD extract (200 mg/kg per day) given orally for 8 weeks. Macroscopic and histopathological evaluation of cartilage lesions and immunohistochemical analysis of cartilage to assess levels of inducible nitric oxide synthase (iNOS), matrix metalloprotease 13 (MMP-13) and protease activated receptor 2 (PAR-2) were done. A gait analysis of dogs was performed.


RESULTS
Treatment with BCD reduced the severity (depth) (p=0.04) and histopathological score (p<0.02) of osteoarthritis cartilage lesions. BCD treatment also significantly reduced the osteoarthritis chondrocyte level of key inflammatory and catabolic factors (iNOS, p=0.009 and MMP-13, p=0.003) as well as the level of PAR-2 (p=0.03). Dogs treated with BCD showed a significant improvement in peak vertical force measured at 8 weeks (p<0.05).


CONCLUSIONS
Treatment with BCD extract exerts a positive effect on the prevention of cartilage lesions induced by joint instability, and improves joint function. This effect was associated with the inhibition of major catabolic and inflammatory mediators. This study is the first to demonstrate that a therapeutic intervention that can inhibit PAR-2 is associated with a disease-modifying osteoarthritis effect.
Boileau
Christelle
C
Osteoarthritis Research Unit, University of Montreal Hospital Research Centre, CR-CHUM, Notre-Dame Hospital, 1560 Sherbrooke Street East, JA de Sève Pavilion, 2nd floor, Montreal, Quebec H2L 4M1, Canada.
Martel-Pelletier
Johanne
J
Caron
Judith
J
Paré
Frédéric
F
Troncy
Eric
E
Moreau
Maxim
M
Pelletier
Jean-Pierre
JP
D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D029748:Caryophyllaceae; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005684:Gait; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D010936:Plant Extracts; D044464:Receptor, PAR-2