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
- Christelle Boileau1,
- Johanne Martel-Pelletier1,
- Judith Caron1,
- Frédéric Paré1,
- Eric Troncy2,
- Maxim Moreau2,3,
- Jean-Pierre Pelletier1
- 1Osteoarthritis Research Unit, University of Montreal Hospital Research Centre, CR-CHUM, Notre-Dame Hospital, Montreal, Quebec, Canada
- 2GREPAQ – Department of Veterinary Biomedicine, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, Quebec, Canada
- 3The Companion Animal Research Group, Department of Clinical Science, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, Quebec, Canada
- Correspondence to Professor Jean-Pierre Pelletier, 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;
- Accepted 9 June 2009
- Published Online First 21 June 2009
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.
Funding This study was funded in part by a grant from Vita Green Pharmaceutical (HK) Limited. Vita Green Pharmaceutical (HK) Limited participated in the decision to submit the manuscript for publication but was not involved in the study design, acquisition, analysis and interpretation of data, or the writing of the manuscript.
Competing interests JMP and JPP are consultants for Vita Green Pharmaceutical (HK) Limited.
Ethics approval The study protocol was approved by the institutional ethics committee and conducted according to the Canadian Council for Animal Care guidelines.
Provenance and peer review Not commissioned; externally peer reviewed.