ABSTRACT
Objective: This study was to examine the anti-inflammatory effect of sappanone A on interleukin- (IL-) 1ß-stimulated osteoarthritis (OA) chondrocytes. Methods: Chondrocytes were pretreated with sappanone A for 2 h before subsequent IL-1ß stimulation. The mRNA expression levels of iNOs, COX-2, aggrecan, and collagen-II were measured with qRT-PCR. The levels of TNF-α, IL-6, IL-8, MMP-3, and MMP-13 were determined by ELISA. The protein levels of iNOs, COX-2, ADAMTS-4, ADAMTS-5, aggrecan, collagen-II, p-p65, p65, IκBα, Nrf2, and HO-1 were assessed by Western blot. Results: Sappanone A inhibited the IL-1ß-stimulated production of NO, PGE2, iNOS, COX-2, TNF-α, IL-6, and IL-8 in OA chondrocytes. In addition, sappanone A suppressed the expression of MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 in IL-1ß-stimulated OA chondrocytes. The degradation of ECM components was reversed by sappanone A. Sappanone A prevented NF-κB activation while enhanced Nrf2/HO-1 activation in IL-1ß-treated chondrocytes. Conclusion: Sappanone A may be a potent therapeutic agent for OA.
Subject(s)
Chondrocytes , Osteoarthritis , Aggrecans/metabolism , Aggrecans/pharmacology , Anti-Inflammatory Agents/therapeutic use , Chondrocytes/metabolism , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/pharmacology , Cyclooxygenase 2/therapeutic use , Dinoprostone/metabolism , Dinoprostone/pharmacology , Dinoprostone/therapeutic use , Humans , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Interleukin-8/metabolism , Isoflavones , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 13/pharmacology , Matrix Metalloproteinase 3/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , NF-KappaB Inhibitor alpha/metabolism , NF-kappa B/metabolism , Osteoarthritis/drug therapy , Osteoarthritis/metabolism , RNA, Messenger/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Objective@#To investigate the incidence of malnutrition in children and adolescents aged between 8 and 16 years in Zhongshan, Guangdong Province and to explore the impact of lower body mass index in early childhood on malnutrition in children and adolescents.@*Methods@#A retrospective cohort of 2 188 students with complete data on weight and height from grade one in primary school to grade one in high school in Zhongshan were included in this analysis. Normal weight individuals with BMI lower than the 50th percentiles (P50) were defined as lower BMI, according to "Report on the Physical Fitness and Health Surveillance of Chinese School Students" in 2005. Screening Standard for Malnutrition of School-age Children and Adolescents in 2014 (WS/T 456—2014) was used to define malnutrition. Prevalence and incidence of malnutrition was calculated, and chi-square test was used to compare the difference of the incidence of malnutrition between children with BMI <P50 and those with BMI ≥P50 at baseline.@*Results@#The prevalence of malnutrition was 15.08% for children in grade one of primary school, which reached highest of 16.32% in grade two of primary school and decreased to 7.27% in grade one in high school. The annual incidence of malnutrition among students with normal weight decreased from 8.37% in grade two in primary school to 1.22% in grade one in high school. Boys with lower BMI in grade one in primary school had the incidence of malnutrition with 12.47% in grade two in primary school, while those with BMI ≥P50 had the incidence of 0.63%. Girls with lower BMI had higher incidence of malnutrition than those with BMI ≥P50.@*Conclusion@#Incident malnutrition between grade one in primary school and grade one in high school is more likely to occur in early childhood. Lower BMI in early childhood significantly increases the risk of malnutrition in children and adolescents. Malnutrition prevention should be implemented from early childhood, especially for those with lower BMI.
ABSTRACT
Osteoarthritis (OA) is one of the most characterized joint diseases associated with chondrocyte apoptosis. JNK plays an important role in apoptosis in many pathological conditions, but systemic inhibition of JNK was shown to result in detrimental side effects. MAPK kinase 7 (MKK7) is a direct upstream kinase that regulates JNK and has been shown to activate JNK specifically under toxic conditions. In this study, we investigated the effect of GADD45ß-I, a cell-permeable inhibitor targeted for MKK7, on IL-1ß-induced cytotoxicity in rat chondrocytes. The results showed that IL-1ß exposure resulted in toxicity in a dose-dependent manner, which was nullified by endoplasmic reticulum (ER) stress inhibitors. GADD45ß-I significantly preserved cell survival, inhibited oxidative injury and reduced apoptosis after IL-1ß treatment. ER stress in chondrocytes was attenuated by GADD45ß-I, as evidenced by reduced levels of GRP78 and CHOP, as well as decreased caspase-12 cleavage. In addition, GADD45ß-I increased the enzymatic activities of mitochondrial antioxidant enzymes, including IDH2, GSH-Px and SOD2. GADD45ß-I significantly upregulated the expression of Sirt3 and attenuated IL-1ß-induced acetylation of SOD2. Furthermore, GADD45ß-I-induced inhibition of ER stress and protection in chondrocytes were partially reversed by knockdown of Sirt3. In conclusion, our data indicated that GADD45ß-I protected chondrocytes against IL-1ß through Sirt3-mediated inhibition of ER stress. Targeting MKK7 might be an ideal therapeutic strategy for reducing chondrocyte apoptosis in OA.
