Prophylactic treatment with S100A9 inhibitor paquinimod reduces pathology in experimental collagenase-induced osteoarthritis.
OBJECTIVES
Alarmins S100A8/A9 regulate pathology in experimental osteoarthritis (OA). Paquinimod is an immunomodulatory compound preventing S100A9 binding to TLR-4. We investigated the effect of paquinimod on experimental OA and human OA synovium.


MATERIALS AND METHODS
Two OA mouse models differing in level of synovial activation were treated prophylactic with paquinimod. Synovial thickening, osteophyte size and cartilage damage were measured histologically, using an arbitrary score, adapted Pritzker OARSI score or imaging software, respectively. Human OA synovia were stimulated with S100A9, with or without paquinimod.


RESULTS
Paquinimod treatment of collagenase-induced OA (CIOA) resulted in significantly reduced synovial thickening (57%), osteophyte size at the medial femur (66%) and cruciate ligaments (67%) and cartilage damage at the medial tibia (47%) and femur (75%; n=7, untreated n=6). In contrast, paquinimod did not reduce osteophyte size and reduced cartilage damage at one location only in destabilised medial meniscus, an OA model with considerably lower synovial activation compared with CIOA. In human OA synovium, paquinimod blocked proinflammatory (interleukin (IL)-6, IL-8, tumour necrosis factor-α) and catabolic (matrix metalloproteinases 1 and 3) factors induced by S100A9 (n=5).


CONCLUSIONS
Prophylactic treatment of paquinimod reduces synovial activation, osteophyte formation and cartilage damage in experimental OA with high synovial activation (CIOA) and ameliorates pathological effects of S100A9 in OA synovium ex vivo.
['Schelbergen|R F|RF|', 'Geven|E J|EJ|', 'van den Bosch|M H J|MH|', 'Eriksson|H|H|', 'Leanderson|T|T|', 'Vogl|T|T|', 'Roth|J|J|', 'van de Loo|F A J|FA|', 'Koenders|M I|MI|', 'van der Kraan|P M|PM|', 'van den Berg|W B|WB|', 'Blom|A B|AB|', 'van Lent|P L E M|PL|']
D000818:Animals D001169:Arthritis, Experimental D040502:Calgranulin B D002358:Cartilage, Articular D017364:Collagenases D004195:Disease Models, Animal D006801:Humans D007166:Immunosuppressive Agents D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D011804:Quinolines D013583:Synovial Membrane
Osteoarthritis Inflammation Synovitis