Department of Biochemistry, Pain Research Center, School of Medicine, Keimyung University, Daegu, Republic of Korea.
Rheumatol Int. 2012 Feb;32(2):379-85. doi: 10.1007/s00296-010-1641-9. Epub 2010 Nov 28.
Very recently, the circadian rhythm was proved to play an important role in the pathogenesis of arthritis. The role of melatonin in the development and progress of rheumatoid arthritis has been implicated for decades. This study was aimed to investigate the effect of melatonin on the expression of circadian clock genes in mouse anti-type II collagen antibody-induced arthritis (CIA). Mice were divided into 3 groups: control, CIA, and CIA + melatonin treatment (MLT). Both mRNA and protein levels of circadian clock gene Cryptochrome1 (Cry1) were markedly decreased in CIA + MEL group compared with those in control and CIA groups. MLT increased paw thickness. Histologic and X-ray assessment also revealed increased infiltration of inflammatory cells, synovial hyperplasia, and the destruction of articular cartilage and bone by MLT. The concentrations of anti-type II collagen antibody in CIA + MEL group mice were significantly higher than those in control and CIA groups (P < 0.05). Serum concentrations of TNF-α (P < 0.005) and IL-6 (P < 0.05) in CIA + MLT group were also increased. Taken together, these results implicate that clock gene Cry1 may be involved in the aggravation of MLT-mediated arthritis in mice anti-type II collagen antibody-induced arthritis.
最近，昼夜节律被证明在关节炎的发病机制中起着重要作用。褪黑素在类风湿关节炎的发展和进展中的作用已经被牵连了几十年。本研究旨在探讨褪黑素对小鼠抗 II 型胶原抗体诱导关节炎（CIA）中昼夜节律基因表达的影响。小鼠分为 3 组：对照组、CIA 组和 CIA+褪黑素治疗（MLT）组。与对照组和 CIA 组相比，CIA+MEL 组的昼夜节律基因 Cryptochrome1（Cry1）的 mRNA 和蛋白水平明显降低。MLT 增加了爪厚度。组织学和 X 射线评估还显示，通过 MLT 增加了炎症细胞的浸润、滑膜增生以及关节软骨和骨的破坏。CIA+MEL 组小鼠的抗 II 型胶原抗体浓度明显高于对照组和 CIA 组（P<0.05）。CIA+MLT 组的血清 TNF-α（P<0.005）和 IL-6（P<0.05）浓度也升高。综上所述，这些结果表明，时钟基因 Cry1 可能参与了 MLT 介导的关节炎在小鼠抗 II 型胶原抗体诱导关节炎中的加重。
