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Published in: Arthritis Research & Therapy 1/2014

Open Access 01-02-2014 | Research article

Increased physical activity severely induces osteoarthritic changes in knee joints with papain induced sulfate-glycosaminoglycan depleted cartilage

Authors: Michiel Siebelt, Harald C Groen, Stuart J Koelewijn, Erik de Blois, Marjan Sandker, Jan H Waarsing, Cristina Müller, Gerjo JVM van Osch, Marion de Jong, Harrie Weinans

Published in: Arthritis Research & Therapy | Issue 1/2014

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Abstract

Introduction

Articular cartilage needs sulfated-glycosaminoglycans (sGAGs) to withstand high pressures while mechanically loaded. Chondrocyte sGAG synthesis is regulated by exposure to compressive forces. Moderate physical exercise is known to improve cartilage sGAG content and might protect against osteoarthritis (OA). This study investigated whether rat knee joints with sGAG depleted articular cartilage through papain injections might benefit from moderate exercise, or whether this increases the susceptibility for cartilage degeneration.

Methods

sGAGs were depleted from cartilage through intraarticular papain injections in the left knee joints of 40 Wistar rats; their contralateral joints served as healthy controls. Of the 40 rats included in the study, 20 rats remained sedentary, and the other 20 were subjected to a moderately intense running protocol. Animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (μCT) to measure subchondral bone changes and single-photon emission computed tomography (SPECT)/CT to determine synovial macrophage activation. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology to measure sGAG content and cartilage thickness.

Results

All outcome measures were unaffected by moderate exercise in healthy control joints of running animals compared with healthy control joints of sedentary animals. Papain injections in sedentary animals resulted in severe sGAG-depleted cartilage, slight loss of subchondral cortical bone, increased macrophage activation, and osteophyte formation. In running animals, papain-induced sGAG-depleted cartilage showed increased cartilage matrix degradation, sclerotic bone formation, increased macrophage activation, and more osteophyte formation.

Conclusions

Moderate exercise enhanced OA progression in papain-injected joints and did not protect against development of the disease. This was not restricted to more-extensive cartilage damage, but also resulted in pronounced subchondral sclerosis, synovial macrophage activation, and osteophyte formation.
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Metadata
Title
Increased physical activity severely induces osteoarthritic changes in knee joints with papain induced sulfate-glycosaminoglycan depleted cartilage
Authors
Michiel Siebelt
Harald C Groen
Stuart J Koelewijn
Erik de Blois
Marjan Sandker
Jan H Waarsing
Cristina Müller
Gerjo JVM van Osch
Marion de Jong
Harrie Weinans
Publication date
01-02-2014
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2014
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4461

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