Protective effects of total fraction of avocado/soybean unsaponifiables on the structural changes in experimental dog osteoarthritis: inhibition of nitric oxide synthase and matrix metalloproteinase-13.
BACKGROUND
The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament dog model and, second, to explore their mode of action.


METHODS
Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in crossbred dogs. There were two treatment groups (n = 8 dogs/group), in which the animals received either placebo or avocado/soybean unsaponifiables (10 mg/kg per day), which were given orally for the entire duration of the study (8 weeks). We conducted macroscopic and histomorphological analyses of cartilage and subchondral bone of the femoral condyles and/or tibial plateaus. We also conducted immunohistochemical analyses in cartilage for the following antigens: inducible nitric oxide synthase, matrix metalloproteinase (MMP)-1, MMP-13, a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS)4 and ADAMTS5.


RESULTS
The size of macroscopic lesions on the tibial plateaus was decreased (P = 0.04) in dogs treated with the avocado/soybean unsaponifiables. Histologically, in these animals the severity of cartilage lesions on both tibial plateaus and femoral condyles, and the cellular infiltration in synovium were significantly decreased (P = 0.0002 and P = 0.04, respectively). Treatment with avocado/soybean unsaponifiables also reduced loss of subchondral bone volume (P < 0.05) and calcified cartilage thickness (P = 0.01) compared with placebo. Immunohistochemical analysis of cartilage revealed that avocado/soybean unsaponifiables significantly reduced the level of inducible nitric oxide synthase (P < 0.05) and MMP-13 (P = 0.01) in cartilage.


CONCLUSIONS
This study demonstrates that treatment with avocado/soybean unsaponifiables can reduce the development of early osteoarthritic cartilage and subchondral bone lesions in the anterior cruciate ligament dog model of osteoarthritis. This effect appears to be mediated through the inhibition of inducible nitric oxide synthase and MMP-13, which are key mediators of the structural changes that take place in osteoarthritis.
Boileau
Christelle
C
Osteoarthritis Research Unit, University of Montreal Hospital Centre, Notre-Dame Hospital, Sherbrooke Street East, Montreal, Quebec, Canada. christelle.boileau@umontreal.ca
Martel-Pelletier
Johanne
J
Caron
Judith
J
Msika
Philippe
P
Guillou
Georges B
GB
Baudouin
Caroline
C
Pelletier
Jean-Pierre
JP
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002356:Cartilage / Q000187:drug effects / Q000473:pathology; D004285:Dogs; D004338:Drug Combinations; D007150:Immunohistochemistry; D053509:Matrix Metalloproteinase 13 / Q000187:drug effects* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D027421:Persea / Q000737:chemistry*; D010840:Phytosterols / Q000627:therapeutic use*; D010936:Plant Extracts / Q000627:therapeutic use*; D013025:Glycine max / Q000737:chemistry*; D014810:Vitamin E / Q000627:therapeutic use*
D004338:Drug Combinations; D010840:Phytosterols; D010936:Plant Extracts; C003884:piascledine; D014810:Vitamin E; D019001:Nitric Oxide Synthase; D053509:Matrix Metalloproteinase 13