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Abstract Background Sirtuin 1 (SIRT1) is reported downregulated in rheumatoid arthritis (RA), and the protective effects of SIRT1 on tissue damage and organ failure may be related to cellular ferroptosis. However, the exact mechanism by which SIRT1 regulates RA remains unclear. Methods Quantitative real-time PCR (qPCR) and western blot assays were performed to explore the expressions of SIRT1 and Yin Yang 1 (YY1). CCK-8 assay was used for cytoactive detection. The interaction between SIRT1 and YY1 was validated by dual-luciferase reporter gene assay and chromatin immunoprecipitation (ChIP). DCFH-DA assay and iron assay were applied to detect the reactive oxygen species (ROS) and iron ion levels. Results In the serum of RA patients, SIRT1 was downregulated, but YY1 was upregulated. In LPS-induced synoviocytes, SIRT1 could increase cell viability and decrease ROS and iron levels. Mechanistically, YY1 downregulated the expression of SIRT1 by inhibiting its transcription. YY1 overexpression partly revised the effects of SIRT1 on ferroptosis in synoviocytes. Conclusion SIRT1 is transcriptionally repressed by YY1 and inhibits the ferroptosis of synoviocytes induced by LPS, so as to relieve the pathological process of RA. Therefore, SIRT1 might be a new diagnosis and therapeutic target of RA. Highlights Combining SIRT1 with synoviocytes ferroptosis in rheumatoid arthritis for the first time. The transcription factor YY1 combined to the SIRT1 promoter in synovial cells and inhibited its expression and functional roles. The inhibition of SIRT1 with YY1 decreased the ferroptosis in synoviocytes.
ABSTRACT
Objective@#To investigate the age related changes in cervical range of motion (CROM) and its relationship with cervical spondylosis in school students aged 12-18 in Nanyang City, to provide reference for prevention, early diagnosis and treatment evaluation of cervical spondylosis.@*Methods@#Stratified sampling was adopted in 13 counties and districts of Nanyang City and 890 students aged 12-18 were assessed for CROM using the Coda Motion Analyzer. SPSS 19.0 was used to data analyze.@*Results@#A decreasing trend was observed in CROM among boys and girls aged 12-18 years in Nanyang. For boys aged 15 and 18 years old, higher anterior flexion ( t =2.02, 2.70), posterior extension ( t =2.01, 2.81), left flexion ( t =3.51, 2.99), right flexion ( t =5.07, 2.66), sinistral ( t =2.28, 2.92) and dextral ( t =2.91,3.60) were found compared with younger age groups ( P <0.05). Similar findings were found in girls aged 15 and 18-years old [anterior flexion ( t =2.38, 2.20), posterior extension ( t =2.09,2.02), left flexion ( t =2.33, 2.55), right flexion ( t =7.34, 4.60), sinistral ( t =3.73, 2.35) and dextral ( t =2.31, 3.99, P <0.05). Except for the right flexion, the CROM of boys in was higher than that of girls at the same age group. The prevalence of cervical spondylosis showed an increasing trend (boys: χ 2 trend =13.93, girls: χ 2 trend =12.87, P <0.05). Except for 14-year-old group, the prevalence of cervical spondylosis in girls was higher than that in boys, with significant differences observed in 15 and 17-year-old groups ( χ 2=10.35, 9.64, P <0.05).@*Conclusion@#With the increase of age, the CROM of male and female students shows a downward trend in general. The prevalence of cervical spondylosis increases with the decrease of CROM. CROM measurement is conducive to the prevention, early diagnosis and treatment of juvenile cervical spondylosis.