Abstract
BackgroundAlthough osteoarthritis (OA) is a multifactorial disease, little has been reported regarding the cooperative interaction among these factors on cartilage metabolism. Here we examined the synergistic effect of ovariectomy (OVX) and excessive mechanical stress (forced running) on articular cartilage homeostasis in a mouse model resembling a human postmenopausal condition.MethodsMice were randomly divided into four groups, I: Sham, II: OVX, III: Sham and forced running (60 km in 6 weeks), and IV: OVX and forced running. Histological and immunohistochemical analyses were performed to evaluate the degeneration of articular cartilage and synovitis in the knee joint. Morphological changes of subchondral bone were analyzed by micro-CT.ResultsMicro-CT analyses showed significant loss of metaphyseal trabecular bone volume/tissue volume (BV/TV) after OVX as described previously. Forced running increased the trabecular BV/TV in all mice. In the epiphyseal region, no visible alteration in bone morphology or osteophyte formation was observed in any of the four groups. Histological analysis revealed that OVX or forced running respectively had subtle effects on cartilage degeneration. However, the combination of OVX and forced running synergistically enhanced synovitis and articular cartilage degeneration. Although morphological changes in chondrocytes were observed during OA initiation, no signs of bone marrow edema were observed in any of the four experimental groups.ConclusionWe report the coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration. Since no surgical procedure was performed on the knee joint directly in this model, this model is useful in addressing the molecular pathogenesis of naturally occurring OA.
Highlights
Osteoarthritis (OA) is a multifactorial disease, little has been reported regarding the cooperative interaction among these factors on cartilage metabolism
We examined the effect of extensive treadmill exercise and ovariectomy (OVX) on articular cartilage homeostasis, both of which have been indicated as risk factors for human OA
We consider that this model is useful in addressing the molecular pathogenesis of naturally occurring OA since surgical procedure was not performed directly on the knee joint
Summary
Osteoarthritis (OA) is a multifactorial disease, little has been reported regarding the cooperative interaction among these factors on cartilage metabolism. Synoviocytes are metabolically highly active cells residing in the synovial membrane and are considered physiologically prerequisite for joint homeostasis as they nourish chondrocytes via synovial fluid and remove metabolites and matrix degradation products from joint space. In an inflammatory environment, it is reported that these cells express catabolic and proinflammatory mediators such as cytokines, nitric oxide, prostaglandin E2, and neuropeptides, which leads to excess production of the proteolytic enzymes responsible for cartilage degeneration [16]. These evidences suggest the relevance of obesity, inflammation, and estrogen signal in disease pathogenesis
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