Melatonin attenuates clock gene cryptochrome1, which may aggravate mouse anti-type II collagen antibody-induced arthritis.
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.
Department of Biochemistry, Pain Research Center, School of Medicine, Keimyung University, Daegu, Republic of Korea.
Jihye
J
Bang
Hyuk Won
HW
Chang
Hae-Ra
HR
Jung
Chul-Hyun
CH
Cho
Ji-An
JA
Hur
Sang-Il
SI
Lee
Tae Hyun
TH
Choi
Sang-Hyon
SH
Kim
Eunyoung
E
Ha
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D056926:CLOCK Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D024043:Collagen Type II / Q000276:immunology / Q000633:toxicity*; D056931:Cryptochromes / Q000037:antagonists & inhibitors / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D008297:Male; D008550:Melatonin / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics; D011897:Random Allocation; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D024043:Collagen Type II; C538964:Cry1 protein, mouse; D056931:Cryptochromes; D012333:RNA, Messenger; D056926:CLOCK Proteins; C538944:Clock protein, mouse; D008550:Melatonin