Association between matrix metalloproteinase-1 (MMP-1) protein level and the risk of rheumatoid arthritis and osteoarthritis: a meta-analysis

Recent publications have investigated the potential role of the protein level of matrix metalloproteinase-1 (MMP-1) in the susceptibility to rheumatoid arthritis (RA) and osteoarthritis (OA). However, no unanimous conclusion was obtained. Therefore, we carried out a meta-analysis to explore the association between MMP-1 expression and these two clinical disorders. After database searching and screening, we enrolled a total of eighteen articles for the pooled analysis. We observed a significant association between RA cases and controls in the whole population [SMD (standard mean difference)=1.01, P=0.017]. There were similar positive results in the subgroup analysis of "population-based control" (SMD=1.50, P=0.032) and "synovial fluid" (SMD=1.32, P=0.049). In addition, we observed an increased risk in OA cases, compared with controls, in the overall analysis (SMD=0.47, P=0.004) and subsequent subgroup analysis of "knee OA" (SMD=0.86, P<0.001), "Asian/China" (SMD=0.76, P=0.003), "cartilage-Asian/China" (SMD=1.21, P<0.001), and "synovial fluid-Asian/China" (SMD=0.73, P=0.004). In summary, a high protein level of MMP-1 in synovial fluid may be associated with the susceptibility to RA, and the high MMP-1 level in the cartilage tissue or synovial fluid may be related to the pathogenesis of knee OA in the Chinese population. This should be confirmed by larger sample sizes.

Effects of novel smo inhibitor si-4650 on proliferation, apoptosis and autophagy of human glioma u87mg cells / 中国药理学通报

Aim To investigate the effects of a novel spermine oxidase (SMO) inhibitor SI-4650 on proliferation, apoptosis and autophagy of human glioma U87MG cells as well as its possible mechanism. Methods MIT assay was used to detect cell proliferation. The chemiluminescence assay was used to determine enzyme activities of SMO and N'-acetylpolyamine oxidase (APAO). High performance liquid chromatography (HPI.C) was performed to detect cellular polyamine content. Transwell assay was used to evaluate the migration ability of U87MG cells. PI single-staining/flow cytometry( FCM ) were used to analyze cell cycle. PI/ FITC-Annexin V double-staining/ FCM and Western blot were used to analyze apoptosis. Confocal laser scanning microscopy ( LSCM) and Western blot were used to analyze autophagy. Results SI-4650 could significantly inhibit the activities of SMO and APAO, interfere with polyamine metabolism and reduce the content of total polyamine in U87MG cells. Treatment of U87MG cells with SI-4650 inhibited the proliferation and migration, caused G0/G, cell cycle arrest and induced apoptotic and autophagic cell death. Conclusions SI-4650 has the pharmacological activity of killing glioma U87MG cells, and its mechanism may be related to the interference of polyamine metabolism and induction of cell apoptosis and autophagy.