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

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.

Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression

“…Recently, we established a novel rat OA model using a combination of papain injections with a running protocol which induces severe knee joint articular cartilage degradation together with activation of synovial macrophages and prominent involvement of subchondral bone [25]. In this particular study we found that papain injection alone induced moderate OA features, like sGAG and slight cartilage matrix loss, enhanced loss of the subchondral cortical plate.…”

“…This sequence consisted of a SPECT/CT using a folate-based radiotracer to quantify macrophage activation in vivo [28], and ex vivo EPIC-μCT and histology to measure cartilage quality [29]. For all procedures, the exact same procedures were followed as described earlier [25]. The animal ethic committee of the Erasmus University Medical Center, Rotterdam, the Netherlands, approved all conducted procedures.…”

“…Their right knee joint served as an internal healthy control. All rats were forced to run on a motorized rodent treadmill (LE-8700; Panlab Harvard Apparatus, Barcelona, Spain) 500 m/day during 5 days/week, for six weeks covering a distance of 15 km in total [25].…”

“…Severe osteoarthritis was induced in all animals using intra-articular papain injections in their left knee joints combined with exposure to a moderate exercise protocol as described before [25]. In short, all animals received three intra-articular injections in their left knee joints with 30 μl papain/L-cystein solution [27].…”

“…We used longitudinal in vivo microCT scans to measure effects of ALN treatment on subchondral sclerosis development and ex-vivo microCT on cartilage samples to see if cartilage was protected against degradation. Besides marked changes of articular cartilage and subchondral bone in this model for OA, we know there is also abundant activation of synovial macrophages [25]. Therefore, we also measured whether ALN treatment had an effect on synovial macrophage activation using a folate-based radiotracer for in vivo SPECT/CT imaging [26].…”