A critical role for collagen II in cartilage matrix degradation: Collagen II induces pro-inflammatory cytokines and MMPs in primary human chondrocytes

2009 ◽  
Vol 27 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Andreas R. Klatt ◽  
Brigitte Paul-Klausch ◽  
Gabriele Klinger ◽  
Getrud Kühn ◽  
Joerg H. Renno ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Critical Role ◽  
Cartilage Matrix ◽  
Human Chondrocytes ◽  
Matrix Degradation ◽  
Collagen Ii ◽  
Pro Inflammatory Cytokines

miR-211-5p contributes to chondrocyte differentiation by suppressing Fibulin-4 expression to play a role in osteoarthritis

2019 ◽  
Vol 166 (6) ◽  
pp. 495-502 ◽  
Author(s):  
Hao Liu ◽  
Jun Luo
Keyword(s):  
Inflammatory Cytokines ◽  
Rat Model ◽  
Cartilage Matrix ◽  
Chondrocyte Differentiation ◽  
Matrix Degradation ◽  
Downstream Target ◽  
Promising Target ◽  
Human Disorders ◽  
Pro Inflammatory Cytokines

Abstract MicroRNAs (miRNAs) serve as key regulators in human disorders. Previous research reported that miR-211-5p is down-regulated in osteoarthritis (OA) and that Fibulin-4 inhibits chondrocyte differentiation. However, the role of miR-211-5p in the development of OA has not been clarified, and its downstream target has not been studied. This study aimed to explore the effect of miR-211-5p on chondrocyte differentiation and its influence on OA pathogenesis, as well as the interaction between miR-211-5p and Fibulin-4. In this study, we found that miR-211-5p is significantly down-regulated in articular cartilage tissues in an OA rat model, whereas it is clearly up-regulated during chondrocyte differentiation of ATDC5 cells. Silencing miR-211-5p in ATDC5 cells had an adverse effect on chondrocyte differentiation. Fibulin-4 was identified as a target of miR-211-5p, and miR-211-5p participated in chondrocyte differentiation by negatively regulating Fibulin-4 expression. In the OA rat model, miR-211-5p overexpression facilitated chondrocyte differentiation, along with the reduced pro-inflammatory cytokines level and the level of proteinases responsible for cartilage matrix degradation. In summary, miR-211-5p promotes chondrocyte differentiation by negatively regulating Fibulin-4 expression, and represses the expression of pro-inflammatory cytokines and proteinases responsible for cartilage matrix degradation in OA. miR-211-5p may serve as a promising target for OA treatment.

scholarly journals Alzheimer's disease and periodontitis - an elusive link

2014 ◽  
Vol 60 (2) ◽  
pp. 173-180 ◽  
Author(s):  
Abhijit N. Gurav
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Cytokines ◽  
Critical Role ◽  
Anaerobic Bacteria ◽  
Systemic Infection ◽  
Low Grade ◽  
Inflammatory Status ◽  
Pro Inflammatory Cytokines

Alzheimer's disease is the preeminent cause and commonest form of dementia. It is clinically characterized by a progressive descent in the cognitive function, which commences with deterioration in memory. The exact etiology and pathophysiologic mechanism of Alzheimer's disease is still not fully understood. However it is hypothesized that, neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease. Alzheimer's disease is marked by salient inflammatory features, characterized by microglial activation and escalation in the levels of pro-inflammatory cytokines in the affected regions. Studies have suggested a probable role of systemic infection conducing to inflammatory status of the central nervous system. Periodontitis is common oral infection affiliated with gram negative, anaerobic bacteria, capable of orchestrating localized and systemic infections in the subject. Periodontitis is known to elicit a "low grade systemic inflammation" by release of pro-inflammatory cytokines into systemic circulation. This review elucidates the possible role of periodontitis in exacerbating Alzheimer's disease. Periodontitis may bear the potential to affect the onset and progression of Alzheimer's disease. Periodontitis shares the two important features of Alzheimer's disease namely oxidative damage and inflammation, which are exhibited in the brain pathology of Alzheimer's disease. Periodontitis can be treated and hence it is a modifiable risk factor for Alzheimer's disease.

scholarly journals Cotransfected human chondrocytes: over-expression of IGF-I and SOX9 enhances the synthesis of cartilage matrix components collagen-II and glycosaminoglycans

2015 ◽  
Vol 48 (12) ◽  
pp. 1063-1070 ◽  
Author(s):  
M. Simental-Mendía ◽  
J. Lara-Arias ◽  
E. Álvarez-Lozano ◽  
S. Said-Fernández ◽  
A. Soto-Domínguez ◽  
...  
Keyword(s):  
Cartilage Matrix ◽  
Human Chondrocytes ◽  
Over Expression ◽  
Igf I ◽  
Collagen Ii ◽  
Matrix Components

Abstract 1123: Critical Role Of Adipose Senescence In Insulin Resistance And Vascular Dysfunction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Masayuki Orimo ◽  
Tohru Minamino ◽  
Hideyuki Miyauchi ◽  
Kaoru Tateno ◽  
Sho Okada ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Inflammatory Cytokines ◽  
Cellular Senescence ◽  
Vascular Dysfunction ◽  
Critical Role ◽  
Serum Levels ◽  
P53 Expression ◽  
Deficient Mice ◽  
Pro Inflammatory Cytokines

Cellular senescence is originally described as the finite replicative lifespan of human somatic cells in culture. As a consequence of semi-conservative DNA replication, the extreme terminals of the chromosomes are not duplicated completely, resulting in successive shortening of telomeres with each cell division. Telomerase is a ribonucleoprotein that adds telomeres to the ends of chromosomes. Critically short telomeres are thought to trigger DNA damage response, thereby inducing cellular senescence. Accumulating evidence has suggested that senescent cells promote aging phenotypes or age-related pathologies. Here we show that adipose senescence is critically involved in the regulation of insulin resistance that underlies age-associated cardiovascular disease. The later generation of telomerase-deficient mice with short telomeres exhibited insulin resistance and vascular dysfunction when fed on a high-calorie diet. Adipose tissue of these mice revealed senescence-like phenotypes such as an increase in neutral β galactosidase activity and upregulation of p53 and pro-inflammatory cytokines. Serum levels of pro-inflammatory cytokines were markedly elevated in telomerase-deficient mice and treatment of these mice with a neutralizing antibody against TNF-α significantly improved insulin and glucose intolerance. Removal of senescent adipose tissue reduced serum levels of pro-inflammatory cytokines and thereby improved insulin resistance in telomerase-deficient mice. Conversely, implantation of senescent adipose tissue to wild-type mice impaired insulin sensitivity and glucose tolerance in recipients. Introduction of telomere dysfunction to young adipose tissue markedly upregulated p53 expression and increased the production of pro-inflammatory cytokines. Inhibition of p53 activity significantly improved senescence-like phenotypes of adipose tissue, insulin resistance, and vascular dysfunction in telomerase-deficient mice. These results disclose a novel mechanism of insulin resistance and suggest that adipose senescence is a potential therapeutic target for the treatment of diabetes and diabetic vasculopathy.

scholarly journals Effect of Inflammatory Signaling on Human Articular Chondrocyte Hypertrophy: Potential Involvement of Tissue Repair Macrophages

Cartilage ◽  
2021 ◽  
pp. 194760352110219
Author(s):  
Mauricio N. Ferrao Blanco ◽  
Yvonne M. Bastiaansen-Jenniskens ◽  
Mark G. Chambers ◽  
Andrew A. Pitsillides ◽  
Roberto Narcisi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Cytokines ◽  
Tissue Repair ◽  
Articular Chondrocytes ◽  
Human Articular Chondrocytes ◽  
Human Chondrocytes ◽  
Articular Chondrocyte ◽  
Inflammatory Signaling ◽  
Chondrocyte Hypertrophy ◽  
Pro Inflammatory Cytokines

Objective In osteoarthritis, chondrocytes tend to acquire a hypertrophic phenotype, which contributes to the modification of the extracellular matrix, resulting in permanent cartilage changes. In mouse chondrocytes, pro-inflammatory macrophages and pro-inflammatory cytokines have been shown to stimulate hypertrophy via the activation of the nuclear factor kappa B (NF-κB) pathway. Whether or not this also occurs in human chondrocytes remains unclear. We therefore aimed to investigate whether hypertrophy-like responses in human cartilage are driven mainly by intrinsic inflammatory signaling or shaped by specific macrophage populations. Design Human articular chondrocytes were cultured with pro-inflammatory cytokines or medium conditioned by defined macrophage subsets. Furthermore, the effect of inhibition of NF-κB-dependent gene expression was evaluated using the NF-κB inhibitor SC-514. Hypertrophy was assessed by measuring the transcription level of alkaline phosphatase ( ALPL), type X collagen ( COL10A1), Indian hedgehog ( IHH), and runt-related transcription factor 2 ( RUNX2). Results The expression of hypertrophic genes was not promoted in human chondrocytes by pro-inflammatory cytokines neither pro-inflammatory M(IFNγ + TNFα) macrophages. Inhibition of the NF-κB-dependent gene expression did not affect human articular chondrocyte hypertrophy. However, tissue repair M(IL4) macrophages induced hypertrophy by promoting the expression of COL10A1, RUNX2, and IHH. Conclusion Intrinsic inflammatory signaling activation is not involved in the hypertrophic shift observed in human articular chondrocytes cultured in vitro. However, tissue repair macrophages may contribute to the onset of this detrimental phenotype in human osteoarthritic cartilage, given the effect observed in our experimental models.

scholarly journals Niacin Modulates Pro-inflammatory Cytokine Secretion. A Potential Mechanism Involved in its Anti-atherosclerotic Effect

2013 ◽  
Vol 7 (1) ◽  
pp. 90-98 ◽  
Author(s):  
Pedro Saul Lipszyc ◽  
Graciela Alicia Cremaschi ◽  
María Zorrilla Zubilete ◽  
Maria Laura Aón Bertolino ◽  
Francisco Capani ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Plasma Cholesterol ◽  
Critical Role ◽  
Atherogenic Diet ◽  
Chow Diet ◽  
Potential Contribution ◽  
Pro Inflammatory Cytokines

The pathogenesis of atherosclerosis includes the assignment of a critical role to cells of the monocyte/macrophage lineage and to pro-inflammatory cytokines. Niacin is known to improve lipid metabolism and to produce beneficial modification of cardiovascular risk factors. The aim of this work was to investigate if Niacin is able to modulate pro-inflammatory cytokine production in macrophages in a murine model of atherosclerosis. For this purpose C57Bl/6J mice fed with atherogenic diet (AGD) or with conventional chow diet were used. The AGD group showed an increase in body weight and in total plasma cholesterol, with no differences in triglyceride or HDL levels. Lesions in arterial walls were observed. The characterization of Niacin receptor showed an increase in the receptor number of macrophages from the AGD group. Macrophages from control and AGD animals treated in vitro with an inflammatory stimulus showed elevated levels of IL-6, IL-1 and TNF-α, that were even higher in macrophages from AGD mice. Niacin was able to decrease the production of pro-inflammatory cytokines in stimulated macrophages. Similar effect of Niacin was observed in an in vivo model of inflammation. These results show an attenuating inflammatory mechanism for this therapeutic agent and would point out its potential action in plaque stabilization and in the prevention of atherosclerosis progression. Furthermore, the present results provide the basis for future studies on the potential contribution of Niacin to anti-inflammatory therapies.

The extract of Acanthopanacis Cortex relieves the depression-like behavior and modulates IL-17 signaling in chronic mild stress-induced depressive mice

2021 ◽  
Author(s):  
Lu Yan ◽  
Yiyun Qian ◽  
Chuhan Liu ◽  
Zhanzhan Liu ◽  
Pingping Song ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Neurotrophic Factors ◽  
Critical Role ◽  
Chronic Mild Stress ◽  
Underlying Mechanism ◽  
Signaling Cascade ◽  
Interleukin 17 ◽  
Mild Stress ◽  
Inflammatory Modulation ◽  
Pro Inflammatory Cytokines

Abstract Background: Acanthopanacis Cortex (AC) is a valuable Chinese herbal medicine in Eleutherococcus Maxim., which has the effects of immune inflammatory modulation, anti-stress, anti-fatigue, sedation and analgesia. The functions of herbs from Eleutherococcus Maxim. involve neuroactivity, anti-fatigue, anti-stress and immune inflammatory modulation, and the peripheral functions of which are consistent with AC. However, the central nervous system function of AC has not been clearly illustrated. Since immune inflammatory modulation plays a critical role in the treatment of depression. In this study, we investigated the effect of AC against depression through immune inflammatory modulation.Methods: Chronic mild stress (CMS)-induced depressive mice were used to evaluate the effect of AC against depression. Behavior study and detection of neurotransmitters, neurotrophic factors and pro-inflammatory cytokines were carried out in the study. Interleukin-17 (IL-17) signaling cascade was involved to further study the underlying mechanism of AC against depression.Results: AC had a beneficial effect on CMS-induced depressive mice, including improvement in depressive behavior and modulation of the levels of neurotransmitters, neurotrophic factors and pro-inflammatory cytokines. Moreover, AC was able to suppress IL-17-midiated signaling cascade and thereby alleviating neuroinflammation and depression.Conclusions: Our results revealed that AC showed great effects on anti-depression through immune inflammatory modulation. These findings provide an insight into anti-depression therapy, which will be useful for the development of clinical application of AC.

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