Light alteration affects the internal environment and metabolic homeostasis of the body through circadian rhythm disorders (CRD). CRD is one of the factors that induce and accelerate osteoarthritis (OA). Therefore, the aim of this study was to evaluate the effects of continuous dark-light (DL) cycle on joint inflammation, bone structure, and metabolism in normal and OA Sprague-Dawley (SD) rats. Interleukin (IL)-1β, IL-6, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α were used to evaluate the systemic inflammation in rats. The pathological changes and inflammatory reactions of the cartilage and synovium of the knee joint in rats were evaluated by Safranin O-fast green and immunological staining. Bone turnover was assessed by histomorphometry and μCT scanning, as well as bone metabolism markers and proteins. The expression changes of clock proteins BMAL1, NR1D1, PER3, and CRY1 in representative tissues were detected by western blotting. DL cycle significantly inhibited body weight gain in normal and OA rats. The levels of proinflammatory factors in the peripheral blood circulation and degradation enzymes in the cartilage were significantly decreased in OA+DL rats. DL cycle significantly destroyed the structure of subchondral bone in hindlimbs of OA rats and reduced trabecular bone numbers. The decrease of bone mineral density (BMD), percent bone volume with respect to total bone volume (BV/TV), trabecular number (TB.N), osteoclast number, and mineralization could also be found. The ratio of the receptor activator of nuclear factor-kappa B ligand/osteoprotegerin (RANKL/OPG) in the bone marrow of OA rats was markedly increased under DL, along with the activation of the mononuclear/phagocyte system. The expression of representative clock proteins and genes BMAL1, PER3, and CRY1 were markedly changed in the tissues of OA+DL rats. These results suggested that DL cycle dampened the arthritis and promoted bone resorption and bone mass loss. DL cycle affects bone turnover by regulating osteoclast production in osteoarthritic rats.

中文翻译：

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暗光循环破坏骨代谢并抑制骨关节炎大鼠的关节恶化

光照变化通过昼夜节律紊乱 (CRD) 影响身体的内部环境和代谢稳态。CRD是诱发和加速骨关节炎(OA)的因素之一。因此，本研究的目的是评估连续暗光 (DL) 循环对正常和 OA Sprague-Dawley (SD) 大鼠的关节炎症、骨结构和代谢的影响。白细胞介素 (IL)-1β、IL-6、诱导型一氧化氮合酶 (iNOS) 和肿瘤坏死因子 (TNF)-α 用于评估大鼠的全身炎症。用番红O-fast green和免疫学染色评价大鼠膝关节软骨和滑膜的病理变化和炎症反应。通过组织形态计量学和μCT扫描以及骨代谢标志物和蛋白质评估骨转换。Western blotting检测代表性组织中时钟蛋白BMAL1、NR1D1、PER3和CRY1的表达变化。DL 周期显着抑制正常和 OA 大鼠的体重增加。OA+DL大鼠外周血循环中促炎因子和软骨降解酶水平显着降低。DL循环显着破坏OA大鼠后肢软骨下骨结构，减少骨小梁数量。还可以发现骨矿物质密度 (BMD)、骨体积相对于总骨体积的百分比 (BV/TV)、小梁数 (TB.N)、破骨细胞数和矿化的降低。DL下OA大鼠骨髓中核因子-κB配体/骨保护素受体激活剂（RANKL/OPG）的比例显着升高，随着单核/吞噬细胞系统的激活。代表性时钟蛋白和基因BMAL1、PER3和CRY1在OA+DL大鼠组织中的表达发生显着变化。这些结果表明，DL 循环抑制了关节炎并促进了骨吸收和骨量减少。DL 周期通过调节骨关节炎大鼠中破骨细胞的产生来影响骨转换。