Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

Open Access Highly Accessed Research article

Forced mobilization accelerates pathogenesis: characterization of a preclinical surgical model of osteoarthritis

C Thomas G Appleton12, David D McErlain34, Vasek Pitelka12, Neil Schwartz5, Suzanne M Bernier16, James L Henry5, David W Holdsworth347 and Frank Beier12*

Author Affiliations

1 CIHR Group in Skeletal Development & Remodeling, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, N6A 5C1, Canada

2 Department of Physiology & Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, N6A 5C1, Canada

3 Imaging Research Laboratories, Robarts Research Institute, London, Ontario, N6A 5C1, Canada

4 Department of Medical Biophysics, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, N6A 5C1, Canada

5 Micheal G DeGroote Institute for Pain Research & Care, McMaster University, Hamilton, Ontario, L8S 4L8, Canada

6 Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, N6A 5C1, Canada

7 Department of Diagnostic Radiology & Nuclear Medicine, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, N6A 5C1, Canada

For all author emails, please log on.

Arthritis Research & Therapy 2007, 9:R13  doi:10.1186/ar2120

Published: 6 February 2007

Abstract

Preclinical osteoarthritis (OA) models are often employed in studies investigating disease-modifying OA drugs (DMOADs). In this study we present a comprehensive, longitudinal evaluation of OA pathogenesis in a rat model of OA, including histologic and biochemical analyses of articular cartilage degradation and assessment of subchondral bone sclerosis. Male Sprague-Dawley rats underwent joint destabilization surgery by anterior cruciate ligament transection and partial medial meniscectomy. The contralateral joint was evaluated as a secondary treatment, and sham surgery was performed in a separate group of animals (controls). Furthermore, the effects of walking on a rotating cylinder (to force mobilization of the joint) on OA pathogenesis were assessed. Destabilization-induced OA was investigated at several time points up to 20 weeks after surgery using Osteoarthritis Research Society International histopathology scores, in vivo micro-computed tomography (CT) volumetric bone mineral density analysis, and biochemical analysis of type II collagen breakdown using the CTX II biomarker. Expression of hypertrophic chondrocyte markers was also assessed in articular cartilage. Cartilage degradation, subchondral changes, and subchondral bone loss were observed as early as 2 weeks after surgery, with considerable correlation to that seen in human OA. We found excellent correlation between histologic changes and micro-CT analysis of underlying bone, which reflected properties of human OA, and identified additional molecular changes that enhance our understanding of OA pathogenesis. Interestingly, forced mobilization exercise accelerated OA progression. Minor OA activity was also observed in the contralateral joint, including proteoglycan loss. Finally, we observed increased chondrocyte hypertrophy during pathogenesis. We conclude that forced mobilization accelerates OA damage in the destabilized joint. This surgical model of OA with forced mobilization is suitable for longitudinal preclinical studies, and it is well adapted for investigation of both early and late stages of OA. The time course of OA progression can be modulated through the use of forced mobilization.