Objective. Sirtuin 6 (SIRT-6) is an NAD؉ -dependent deacetylase and mono-ADP-ribosyltransferase. It is known to interfere with the NF-B signaling pathway and thereby has an antiinflammatory function. Due to the central role of NF-B in rheumatoid arthritis (RA) development, we undertook this study to test our hypothesis that SIRT-6 could have antiarthritic effects.Methods. An adenovirus containing SIRT-6 complementary DNA (Ad-SIRT6) was used to deliver SIRT-6 to human RA fibroblast-like synoviocytes in vitro as well as to mice with collagen-induced arthritis (CIA) in vivo via bilateral intraarticular injections into the ankle joints.Results. In vitro experiments demonstrated that SIRT-6 overexpression suppressed NF-B target gene expression induced by tumor necrosis factor ␣. SIRT-6 overexpression inhibited osteoclast differentiation induced by macrophage colony-stimulating factor and RANKL in bone marrow-derived macrophages. Mice with CIA had an increased incidence of disease and developed arthritis in the hind paws. In contrast, mice injected with Ad-SIRT6 showed attenuated severity of arthritis based on clinical scores, hind paw thickness, and radiographic and pathologic findings. Moreover, the injection of Ad-SIRT6 down-regulated local and systemic levels of proinflammatory cytokines. After induction of CIA, mice injected with Ad-SIRT6 showed significantly decreased arthritis severity, from the onset of clinical signs to the end of the study.Conclusion. These results suggest that blocking the NF-B pathway by SIRT-6 in rheumatoid joints reduces both the inflammatory response and tissue destruction. Therefore, the development of an immunoregulatory strategy based on SIRT-6 may have therapeutic potential for the treatment of RA.
Objective. Insulin-like growth factor binding protein 3 (IGFBP-3) is known to interfere with the NF-B signaling pathway, and it effectively promotes apoptosis in tumor cells by a variety of mechanisms. NF-B activation and apoptosis resistance of fibroblast-like synoviocytes (FLS) play pivotal roles in rheumatoid arthritis (RA). This study was undertaken to evaluate whether IGFBP-3 has antiarthritic effects.Methods. To deliver IGFBP-3, we used an adenovirus containing IGFBP-3 complementary DNA (AdIGFBP-3) or IGFBP-3 mutant that is devoid of IGF binding affinity but retains IGFBP-3 receptor binding ability (AdmtIGFBP-3). The regulatory roles of IGFBP-3 in inflammation and bone destruction were investigated in mice with collagen-induced arthritis (CIA).Results. IGFBP-3 levels were significantly higher in patients with RA than in those with osteoarthritis (OA) and were notably higher in patients with active RA. AdIGFBP-3 suppressed NF-B activation, chemokine production, and matrix metalloproteinase secretion induced by tumor necrosis factor ␣ (TNF␣) in RA FLS. AdIGFBP-3 sensitized RA FLS to TNF␣-induced apoptosis in vitro and also significantly increased apoptosis in an in vivo model of Matrigel implants engrafted into immunodeficient mice. AdIGFBP-3-injected mice with CIA had attenuated arthritis severity and reduced radiologic and pathologic abnormalities. Moreover, AdIGFBP-3 down-regulated local and systemic levels of NF-B-targeted proinflammatory cytokines. Of note, RA FLS and mice with CIA treated with AdmtIGFBP-3 exhibited similar effects as those treated with AdIGFBP-3.Conclusion. Our results suggest that both the inflammatory response and bone destruction are reduced with blockage of NF-B activation and induction of apoptosis in RA FLS by IGFBP-3. Therefore, IGFBP-3 may have therapeutic potential in RA.
The purpose of the study was to analyze the relationship between motivation, psychological euphoria and adherence intention in elders. To achieve this purpose, subjects of this study were sampled 249 dancesports participant from J and K city in Jeonbuk. Data were collected through the self-administrated questionnaires which were used by preceding study. The factor analysis method was used correlation analysis, multiple regression analysis and three-step mediated regression analysis. The results of the analysis are as follows: First, motivation(health, hobby) had positive effects on psychological euphoria(accomplishment, satisfaction). Second, motivation(health, hobby) had positive effects on adherence intention. Third, psychological
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