MT3-MMP (MMP-16) is Downregulated by In Vitro Cytokine Stimulation of Cartilage,but Unaltered in Naturally Occurring Equine Osteoarthritis and Osteochondrosis

Matrix degradation by metalloproteinases is considered a key feature in the loss of articular cartilage seen in many joint diseases. Membrane-type matrix metalloproteinase-3 (MT3-MMP) expression is elevated in human cartilage in end-stage osteoarthritis. We investigated whether MT3-MMP is similarly regulated in cartilage in two naturally occurring arthropathies in vivo and whether proinflammatory cytokines regulate its expression in vitro. MT3-MMP expression was evaluated in cartilage from horses with osteoarthritis and osteochondrosis and compared with age- and site-matched normal cartilage. MT3-MMP also was measured in normal cartilage stimulated with proinflammatory cytokines. MT3-MMP expression was not significantly altered in either osteoarthritis or osteochondrosis cartilage. However, gene expression was significantly downregulated by the addition of recombinant human interleukin-1β, oncostatin M, or tumor necrosis factor-α to normal cartilage explants. The results suggest that MT3-MMP may not have a role in matrix destruction in equine cartilage diseases. Further work is required to characterize its regulation and function.     

Age-related NADPH Oxidase (arNOX) Activity Correlated with Cartilage Degradation and Bony Changes in Age-related Osteoarthritis

The purpose of this study was to investigate the age-related NADPH oxidase (arNOX) activity in patients with age-related knee osteoarthritis (OA). Serum and cartilage arNOX activities were determined using an oxidized ferricytochrome C reduction assay. Full-thickness knee joint cartilages obtained through total knee replacement surgery were graded according to the Outerbridge (OB) classification. Radiographic severity of OA was determined on Knee X-rays according to the Kellgren-Lawrence (K/L) grading system. Cartilage β-galactosidase, HIF-1α, and GLUT-1 expression levels were evaluated as markers for tissue senescence, hypoxia, and glycolysis. Higher arNOX activities occurred with higher levels of cartilage β-galactosidase, HIF-1α, and GLUT-1 (P = 0.002). arNOX activity in cartilages with surface defects (OB grade II, III) was higher than in those without the defects (OB grade 0, I) (P = 0.012). Cartilage arNOX activity showed a positive correlation with serum arNOX activity (r = -0.577, P = 0.023). Serum arNOX activity was significantly higher in the OA subgroup with bilateral ROA than in the OA with no or unilateral ROA (2.449 ± 0.81, 2.022 ± 0.251 nM/mL, respectively, P = 0.019). The results of this study demonstrate that OA itself is not a cause to increase arNOX activities, however, arNOX hyperactivity is related to a high degree of cartilage degradation, and a high grade and extent of ROA in age-related OA.

Graphical Abstract

相似文献   

The modern interleukin-1 superfamily: Divergent roles in obesity

Obesity is now recognised as a chronic, low-grade inflammatory disease contributing to insulin resistance, type 2 diabetes (T2D) and cardiovascular disease (CVD). Multiple mechanisms leading to the low grade inflammation in this setting have been suggested. Due to the complexity and interconnection of inflammatory and metabolic responses, there also remains a need to fully elucidate the inflammatory mechanisms that control obesity and associated metabolic disorders. One important avenue in the field that has gained great attention is the interleukin (IL)-1 superfamily of cytokines that consist of IL-1β, IL-18 and IL-33. IL-1β is well known for its contribution as an inflammatory mediator in obesity contributing to insulin resistance and T2D, whereas the IL-18 and IL-33 cytokines have been shown to oppose metabolic dysregulation. This review will focus on the current understanding of the IL-1 superfamily of cytokines in the setting of obesity and discuss how endogenous feedback loops can be exploited for therapeutic approaches to fight obesity and subsequent cardiometabolic disorders.     

首发重度抑郁症患者血清中促炎物质水平的检测

目的：探讨首发重度抑郁症患者血清中促炎物质IL-1α、IL-6、IL-18、肿瘤坏死因子（ TNF-α）以及血清总补体活性（ CH50）水平的变化,以期对首发抑郁症的诊断有所帮助。方法采用汉密尔顿抑郁量表（HAMD）对首发抑郁症患者进行抑郁评分,采用酶联免疫吸附法（ELISA）检测49例首发重度抑郁症组患者和40例体检健康人正常对照组其血清中IL-1α、IL-6、IL-18、TNF-α及CH50的水平。结果首发重度抑郁症患者血清中IL-6、IL-18、TNF-α及CH50水平与正常对照组差异有统计学意义（P＜0．05）,而IL-1α则无明显差异（P＞0．05）;在首发重度抑郁症男女性别分组中,血清中IL-1α水平差异有统计学意义（P＜0．05）,IL-6、IL-18、TNF-α及CH50水平差异无统计学意义（P＞0．05）。结论细胞因子IL-6、IL-18、TNF-α及CH50可能参与或伴随首发重度抑郁症的发生和发展,可以作为首发重度抑郁症的辅助诊断指标。     

Immunoelectron Microscopic Localization of Plasminogen Activator Inhibitor Type 1 (PAI-1) in Smooth Muscle Cells from Morphologically Normal and Atherosclerotic Human Arteries

Vascular wall fibrinolytic system proteins are believed to play a pivotal role in atherogenesis. Tissue-type plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) influence persistence of luminal thrombi and proteolysis of extracellular matrix, respectively. The major physiologic inhibitor of t-PA and u-PA is plasminogen activator inhibitor type 1 (PAI-1). All three of these fibrinolytic system proteins have been detected in vascular endothelial cells, smooth muscle cells, and macrophages by light microscopic immunohistochemistry. This study was undertaken to delineate, by immunoelectron microscopy, the loci of PAI-1 in smooth muscle cells from intact morphologically normal and atherosclerotic human arteries as well as in isolated and cultured smooth muscle cells from arteries. In intact vessels, PAI-1 immunoreactivity was associated with contractile filaments in cells in both normal and atherosclerotic tissues. Lipid-laden smooth muscle cells in atherosclerotic vessels were mainly of the synthetic phenotype and displayed lesser amounts of PAI-1 associated with rough endoplasmic reticulum and contractile filaments. Isolated smooth muscle cells exhibited either a contractile or synthetic phenotype. In the cells with a contractile phenotype, PAI-1 was associated with the contractile elements, whereas in the cells with a synthetic phenotype, the PAI-1 was associated predominantly with elements of the endoplasmic reticulum. Because PAI-1 is associated predominantly with contractile filaments in smooth muscle cells, the net amount of immunodetectable PAI-1 appears to be greater in contractile compared with synthetic phenotype cells.     

Immunoelectron Microscopic Localization of Plasminogen Activator Inhibitor Type 1 (PAI-1) in Smooth Muscle Cells from Morphologically Normal and Atherosclerotic Human Arteries

Vascular wall fibrinolytic system proteins are believed to play a pivotal role in atherogenesis. Tissue-type plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) influence persistence of luminal thrombi and proteolysis of extracellular matrix, respectively. The major physiologic inhibitor of t-PA and u-PA is plasminogen activator inhibitor type 1 (PAI-1). All three of these fibrinolytic system proteins have been detected in vascular endothelial cells, smooth muscle cells, and macrophages by light microscopic immunohistochemistry. This study was undertaken to delineate, by immunoelectron microscopy, the loci of PAI-1 in smooth muscle cells from intact morphologically normal and atherosclerotic human arteries as well as in isolated and cultured smooth muscle cells from arteries. In intact vessels, PAI-1 immunoreactivity was associated with contractile filaments in cells in both normal and atherosclerotic tissues. Lipid-laden smooth muscle cells in atherosclerotic vessels were mainly of the synthetic phenotype and displayed lesser amounts of PAI-1 associated with rough endoplasmic reticulum and contractile filaments. Isolated smooth muscle cells exhibited either a contractile or synthetic phenotype. In the cells with a contractile phenotype, PAI-1 was associated with the contractile elements, whereas in the cells with a synthetic phenotype, the PAI-1 was associated predominantly with elements of the endoplasmic reticulum. Because PAI-1 is associated predominantly with contractile filaments in smooth muscle cells, the net amount of immunodetectable PAI-1 appears to be greater in contractile compared with synthetic phenotype cells.