Heilongjiang Key Laboratory of Animal Disease Pathogenesis and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University, 600, Changjiang Road, Harbin, 150030, China.
Arthritis Res Ther. 2022 Jun 28;24(1):158. doi: 10.1186/s13075-022-02832-8.
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.
光照改变会通过扰乱昼夜节律（CRD）影响机体的内环境和代谢稳态。CRD 是诱发和加速骨关节炎（OA）的因素之一。因此，本研究旨在评估连续明暗（DL）周期对正常和 OA Sprague-Dawley（SD）大鼠关节炎症、骨结构和代谢的影响。
采用白细胞介素（IL）-1β、IL-6、诱导型一氧化氮合酶（iNOS）和肿瘤坏死因子（TNF）-α评估大鼠的全身炎症。通过番红 O-快绿和免疫染色评估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评估骨转换。采用 Western 印迹检测代表性组织中时钟蛋白 BMAL1、NR1D1、PER3 和 CRY1 的表达变化。
DL 周期显著抑制正常和 OA 大鼠的体重增加。OA+DL 大鼠外周血循环中的促炎因子和软骨降解酶水平显著降低。DL 周期显著破坏 OA 大鼠后肢的软骨下骨结构，减少小梁骨数量。骨密度（BMD）、骨体积/总体积（BV/TV）、小梁数（TB.N）、破骨细胞数量和矿化程度降低。OA 大鼠骨髓中核因子-κB 配体/骨保护素（RANKL/OPG）的比值在 DL 下显著增加，单核/吞噬细胞系统被激活。OA+DL 大鼠组织中代表性时钟蛋白和基因 BMAL1、PER3 和 CRY1 的表达明显改变。
这些结果表明，DL 周期可减轻关节炎并促进破骨和骨量丢失。DL 周期通过调节破骨细胞生成来影响 OA 大鼠的骨转换。
