Coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration.
Coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration.
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DOI：
10.1186/s12891-016-1094-8
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发表时间：
2016-05-31
影响因子：
2.3
通讯作者：
Tsuji K
中科院分区：
文献类型：
--
作者：
Miyatake K;Muneta T;Ojima M;Yamada J;Matsukura Y;Abula K;Sekiya I;Tsuji K
虽然骨关节炎（OA）是一个多因素的疾病，很少有关于这些因素之间的合作相互作用对软骨代谢的报道。在这里，我们研究了卵巢切除术（OVX）和过度的机械应力（强迫运行）对关节软骨稳态的协同作用，在一个类似于人类绝经后条件的小鼠模型。将小鼠随机分为4组，I组：假手术组，II组：去卵巢组，III组：假手术+强迫跑组（6周60 km），IV组：去卵巢+强迫跑组。通过组织学和免疫组织化学分析来评估膝关节软骨的退变和滑膜炎。显微CT观察软骨下骨的形态学变化。Micro-CT分析显示，如前所述，OVX后干骺端骨小梁体积/组织体积（BV/TV）显著丢失。强迫跑可使小鼠小梁BV/TV增加。在骨骺区域，在四个组中的任何一个中均未观察到骨形态或骨赘形成的可见改变。组织学分析表明，OVX或强迫跑步对软骨退变有轻微影响。然而，OVX和强迫跑步的组合协同增强了滑膜炎和关节软骨退变。虽然在OA启动期间观察到软骨细胞的形态学变化，但在四个实验组中的任何一个中均未观察到骨髓水肿的迹象。我们报告了广泛的跑步机运动和卵巢切除术对关节软骨退变的协调和协同作用。由于在该模型中没有直接在膝关节上进行外科手术，因此该模型可用于解决自然发生的OA的分子发病机制。
Although 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. Mice 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. Micro-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. We 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.