Dark-light cycle disrupts bone metabolism and suppresses joint deterioration in osteoarthritic rats

暗光循环扰乱骨关节炎大鼠的骨代谢并抑制关节退化

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作者:Xiaopeng Song, Mingchao Zhao, Jilang Tang, Tianwen Ma, Hui Bai, Xinyu Wang, Lin Liu, Ting Li, Xinyu Xu, Xuanbo Sheng, Binger Zhao, Yingying Wang, Tiantian Wang, Yingchao Guo, Xinmin Zhang, Li Gao

Background

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

Conclusions

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.

Methods

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.

Results

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. Conclusions: 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.

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