MicroRNA-27a alleviates IL-1β-induced inflammatory response and articular cartilage degradation via TLR4/NF-κB signaling pathway in articular chondrocytes

2019 ◽  
Vol 76 ◽  
pp. 105839 ◽  
Author(s):  
Wen-Jun Qiu ◽  
Ming-Ze Xu ◽  
Xiao-dong Zhu ◽  
Yun-Han Ji
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Articular Chondrocytes ◽  
Cartilage Degradation

scholarly journals The ciliary protein IFT88 controls post-natal cartilage thickness and influences development of osteoarthritis

2020 ◽  
Author(s):  
CR Coveney ◽  
L Zhu ◽  
J Miotla-Zarebska ◽  
B Stott ◽  
I Parisi ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cell Biology ◽  
Articular Chondrocytes ◽  
Skeletal Development ◽  
Cartilage Degradation ◽  
Cartilage Thickness ◽  
Tissue Growth ◽  
Calcified Cartilage ◽  
Health And Disease

AbstractMechanical forces are known to drive cellular signalling programmes in cartilage development, health, and disease. Proteins of the primary cilium, implicated in mechanoregulation, control cartilage formation during skeletal development, but their role in post-natal cartilage is unknown. Ift88fl/fl and AggrecanCreERT2 mice were crossed to create a cartilage specific inducible knockout mouse AggrecanCreERT2;Ift88fl/fl. Tibial articular cartilage thickness was assessed, through adolescence and adulthood, by histomorphometry and integrity by OARSI score. In situ cell biology was investigated by immunohistochemistry (IHC) and qPCR of micro-dissected cartilage. OA was induced by destabilisation of the medial meniscus (DMM). Some mice were provided with exercise wheels in their cage. Deletion of IFT88 resulted in a reduction in medial articular cartilage thickness (atrophy) during adolescence from 102.57μm, 95% CI [94.30, 119.80] in control (Ift88fl/fl) to 87.36μm 95% CI [81.35, 90.97] in AggrecanCreERT2;Ift88fl/fl by 8-weeks p<0.01, and adulthood (104.00μm, 95% CI [100.30, 110.50] in Ift88fl/fl to 89.42μm 95% CI [84.00, 93.49] in AggrecanCreERT2;Ift88fl/fl, 34-weeks, p<0.0001) through a reduction in calcified cartilage. Thinning in adulthood was associated with spontaneous cartilage degradation. Following DMM, AggrecanCreERT2;Ift88fl/fl mice had increased OA (OARSI scores at 12 weeks Ift88fl/fl = 22.08 +/− 9.30, and AggrecanCreERT2;Ift88fl/fl = 29.83 +/− 7.69). Atrophy was not associated with aggrecanase-mediated destruction or chondrocyte hypertrophy. Ift88 expression positively correlated with Tcf7l2 and connective tissue growth factor. Cartilage thickness was restored in AggrecanCreERT2;Ift88fl/fl by voluntary wheel exercise. Our results demonstrate that ciliary IFT88 regulates cartilage thickness and is chondroprotective, potentially through modulating mechanotransduction pathways in articular chondrocytes.

Polydatin inhibits the IL-1β-induced inflammatory response in human osteoarthritic chondrocytes by activating the Nrf2 signaling pathway and ameliorates murine osteoarthritis

2018 ◽  
Vol 9 (3) ◽  
pp. 1701-1712 ◽  
Author(s):  
Shangkun Tang ◽  
Qian Tang ◽  
Jialei Jin ◽  
Gang Zheng ◽  
Jianchen Xu ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Osteoarthritic Chondrocytes ◽  
Nrf2 Signaling Pathway ◽  
Prevalent Form

Osteoarthritis (OA), which is characterized by progressive degradation of the articular cartilage, is the most prevalent form of human arthritis.

scholarly journals DAMPs Synergize with Cytokines or Fibronectin Fragment on Inducing Chondrolysis but Lose Effect When Acting Alone

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Lei Ding ◽  
Joseph A. Buckwalter ◽  
James A. Martin
Keyword(s):  
Inflammatory Response ◽  
Synergistic Effect ◽  
Culture Medium ◽  
Articular Chondrocytes ◽  
Weight Bearing ◽  
Primary Cultures ◽  
Cartilage Degradation ◽  
Fibronectin Fragment ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Objective and Design. To investigate whether endogenous damage-associated molecular patterns (DAMPs) or alarmins originated from mitochondria or nucleus stimulates inflammatory response in articular chondrocytes to cause chondrolysis which leads to cartilage degradation featured in posttraumatic osteoarthritis (PTOA).Materials. Primary cultures of bovine or human chondrocytes isolated from cartilage of weight-bearing joints.Treatment. Chondrocytes were subjected to mitochondrial DAMPs (MTDs) or HMGB1, a nuclear DAMP (NuD), with or without the presence of an N-terminal 29 kDa fibronectin fragment (Fn-f) or proinflammatory cytokines (IL-1βand TNF-α). Injured cartilage-conditioned culturing medium containing a mixture of DAMPs was employed as a control. After 24 hrs, the protein expression of cartilage degrading metalloproteinases and iNOS in culture medium or cell lysates was examined with Western blotting, respectively.Results. HMGB1 was synergized with IL-1βin upregulating expression of MMP-3, MMP-13, ADAMTS-5, ADAM-8, and iNOS. Moreover, a moderate synergistic effect was detected between HMGB1 and Fn-f or between MTDs and TNF-αon MMP-3 expression. However, when acting alone, MTDs or HMGB1 did not upregulate cartilage degrading enzymes or iNOS.Conclusion. MTDs or HMGB1 could only stimulate inflammatory response in chondrocytes with the presence of cytokines or Fn-f.

scholarly journals Aging, Cell Senescence, the Pathogenesis and Targeted Therapies of Osteoarthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin-Xin Zhang ◽  
Shi-Hao He ◽  
Xu Liang ◽  
Wei Li ◽  
Tian-Fang Li ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cellular Senescence ◽  
Articular Chondrocytes ◽  
Cartilage Degradation ◽  
Cell Senescence ◽  
Joint Disease ◽  
Epigenetic Alterations ◽  
New Agents ◽  
Key Factor ◽  
Long Time

Osteoarthritis (OA) is a chronic, debilitating joint disease characterized by progressive destruction of articular cartilage. For a long time, OA has been considered as a degenerative disease, while recent observations indicate the mechanisms responsible for the pathogenesis of OA are multifaceted. Aging is a key factor in its development. Current treatments are palliative and no disease modifying anti-osteoarthritis drugs (DMOADs) are available. In addition to articular cartilage degradation, cellular senescence, synovial inflammation, and epigenetic alterations may all have a role in its formation. Accumulating data demonstrate a clear relationship between the senescence of articular chondrocytes and OA formation and progression. Inhibition of cell senescence may help identify new agents with the properties of DMOADs. Several anti-cellular senescence strategies have been proposed and these include sirtuin-activating compounds (STACs), senolytics, and senomorphics drugs. These agents may selectively remove senescent cells or ameliorate their harmful effects. The results from preclinical experiments and clinical trials are inspiring. However, more studies are warranted to confirm their efficacy, safety profiles and adverse effects of these agents.

scholarly journals Interleukin-26 Has Synergistic Catabolic Effects with Palmitate in Human Articular Chondrocytes via the TLR4-ERK1/2-c-Jun Signaling Pathway

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2500
Author(s):  
Yi-Ting Chen ◽  
Chih-Chien Wang ◽  
Chia-Pi Cheng ◽  
Feng-Cheng Liu ◽  
Chian-Her Lee ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Arthritis ◽  
Articular Chondrocytes ◽  
Saturated Fatty Acids ◽  
Signal Transduction Pathway ◽  
Cartilage Degradation ◽  
Cartilage Matrix ◽  
Human Articular Chondrocytes ◽  
Cox 2 ◽  
Interleukin 26

The inflammatory cytokine interleukin-26 (IL-26) is highly expressed in the serum and synovial fluid of patients with inflammatory arthritis. The effect of IL-26 on human articular chondrocytes (HACs) remains unclear. Obesity is associated with disability of patients with rheumatoid arthritis and disease activity in those with ankylosing spondylitis. The saturated free fatty acid palmitate with IL-1β can synergistically induce catabolic effects in HACs. The aim of this study was to evaluate the effects of IL-26 and palmitate in HACs. In this study, palmitate markedly synergizes the IL-26-induced proinflammatory effects and matrix protease, including COX-2, IL-6, and MMP-1, in HACs via the toll-like receptor 4 (TLR4)-ERK1/2-c-Jun signal transduction pathway. The synergistic catabolic effects of palmitate and IL-26 were attenuated by inhibitors of TLR4 (TAK242), ERK1/2 (U0126), or c-Jun (SP600125) in HACs and cartilage matrix. In addition, metformin, a potential inhibitor of TLR4, also decreased expression of COX-2 and IL-6 induced by co-incubation with IL-26 and palmitate. IL-26 and palmitate synergistically induced expression of inflammatory and catabolic mediators, resulting in articular cartilage matrix breakdown. The present study also revealed a possible mechanism and therapeutic targets against articular cartilage degradation by increased saturated fatty acids in patients with inflammatory arthritis.

scholarly journals Down-regulation of microRNA-203a suppresses IL-1β-induced inflammation and cartilage degradation in human chondrocytes through Smad3 signaling

2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Yongbo An ◽  
Guang Wan ◽  
Jingang Tao ◽  
Mingxing Cui ◽  
Qinglan Zhou ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Response ◽  
In Vitro Model ◽  
Joint Inflammation ◽  
Cartilage Degradation ◽  
Inhibitory Effects ◽  
Key Factor ◽  
Ecm Degradation ◽  
Vitro Model

Abstract Osteoarthritis (OA) is a chronic and prevalent degenerative musculoskeletal disorder, which is characterized by articular cartilage degradation and joint inflammation. MicroRNA-203a (miR-203a) has been shown to be involved in multiple pathological processes during OA, but little is known about its function in chondrocyte extracellular matrix (ECM) degradation. In the present study, we aimed to elucidate the effects of miR-203a on articular cartilage degradation and joint inflammation. We observed that the miR-203a level was significantly up-regulated in OA tissues and in an in vitro model of OA, respectively. Inhibition of miR-203a significantly alleviated the interleukin (IL)-1β-induced inflammatory response and ECM degradation in chondrocytes. Moreover, mothers against decapentaplegic homolog 3 (Smad3), a key factor in maintaining chondrocyte homeostasis, was identified as a putative target of miR-203a in chondrocytes. More importantly, inhibition of Smad3 impaired the inhibitory effects of the miR-203a on IL-1β-induced inflammatory response and ECM degradation. Collectively, these results demonstrated that miR-203a may contribute to articular cartilage degradation of OA by targeting Smad3, suggesting a novel therapeutic target for the treatment of OA.

Peiminine inhibits the IL-1β induced inflammatory response in mouse articular chondrocytes and ameliorates murine osteoarthritis

2019 ◽  
Vol 10 (4) ◽  
pp. 2198-2208 ◽  
Author(s):  
Zucheng Luo ◽  
Binbin Zheng ◽  
Bingjie Jiang ◽  
Xinghe Xue ◽  
Enxing Xue ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Response ◽  
Articular Chondrocytes

Osteoarthritis (OA) is a common arthrosis characterized by degeneration and inflammation of articular cartilage.

scholarly journals Retraction: Salvianolic acid B inhibits inflammatory response and cell apoptosis via the PI3K/Akt signaling pathway in IL-1β-induced osteoarthritis chondrocytes

RSC Advances ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 4441-4441
Author(s):  
Laura Fisher
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Akt Signaling ◽  
Salvianolic Acid B ◽  
Signalling Pathway ◽  
Akt Signaling Pathway ◽  
Salvianolic Acid ◽  
Osteoarthritis Chondrocytes

Retraction of ‘Salvianolic acid B inhibits inflammatory response and cell apoptosis via the PI3K/Akt signalling pathway in IL-1β-induced osteoarthritis chondrocytes’ by Bin Zhu et al., RSC Adv., 2018, 8, 36422–36429, DOI: 10.1039/C8RA02418A.

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