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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 (PAR-2)
  1. Christelle Boileau (christelle.boileau{at}umontreal.ca)
  1. Osteoarthritis Research Unit, University of Montreal Hospital Centre (CRCHUM), Canada
    1. Johanne Martel-Pelletier (jm{at}martelpelletier.ca)
    1. Osteoarthritis Research Unit, University of Montreal Hospital Centre (CRCHUM), Canada
      1. Judith Caron (jcaron{at}arthrolab.com)
      1. Osteoarthritis Research Unit, University of Montreal Hospital Centre (CRCHUM), Canada
        1. Frédéric Paré (frederic_pare{at}hotmail.com)
        1. Osteoarthritis Research Unit, University of Montreal Hospital Centre (CRCHUM), Canada
          1. Éric Troncy (eric.troncy{at}umontreal.ca)
          1. Department of Veterinary Biomedicine, Faculty of Veterinary Medicine, University of Montreal, Canada
            1. Maxim Moreau
            1. The Companion Animal Research Group, Faculty of Veterinary Medicine, University of Montreal, Canada
              1. Jean-Pierre Pelletier (dr{at}jppelletier.ca)
              1. Osteoarthritis Research Unit, University of Montreal Hospital Centre (CRCHUM), Canada

                Abstract

                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 (OA) lesions and symptoms in the experimental dog anterior cruciate ligament (ACL) transection model and to document its mechanism of action.

                Methods: OA 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/day) given orally for 8 weeks. Macroscopic and histopathological evaluation of cartilage lesions and immunohistochemical analysis of cartilage to assess levels of iNOS, MMP-13, and protease activated receptor (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 OA cartilage lesions. BCD treatment also significantly reduced the OA 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 significant improvement in peak vertical force measured at 8 weeks (p<0.05).

                Conclusions: Treatment with BCD extract can exert a positive effect on the prevention of cartilage lesions induced by joint instability and improve 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 OA effect.

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