Anticatabolic Effects of Morin through the Counteraction of Interleukin-1β-Induced Inflammation in Rat Primary Chondrocytes

2019 ◽  
Vol 207 (1) ◽  
pp. 21-33 ◽  
Author(s):  
Gyeong-Je Lee ◽  
In-A Cho ◽  
Ji-Su Oh ◽  
Yo-Seob  Seo ◽  
Jae-Seek You ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Cellular Mechanism ◽  
Interleukin 1Β ◽  
Potential Candidate ◽  
Primary Chondrocytes ◽  
Progressive Degeneration ◽  
Herbal Plants ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Morin, a flavonoid isolated from various medicinal herbal plants, has an anti-inflammatory effect. This study aimed to elucidate the anticatabolic effects and cellular mechanism of morin against interleukin-1β (IL-1β) in rat primary chondrocytes. Morin at 10–100 μM did not affect the viability of rat primary chondrocytes. Treatment with morin for 21 days ameliorated the IL-1β-induced decrease in extracellular matrix. Furthermore, treatment with morin attenuated IL-1β-induced proteoglycan loss in the articular cartilage through suppression of catabolic factors, such as matrix metalloproteinases, inflammatory mediators, and pro-inflammatory cytokines. These data indicated that morin exerted anticatabolic effects that can prevent and reduce progressive degeneration of the articular cartilage, and thus may be a potential candidate treatment for osteoarthritis.

scholarly journals Restoration of the Phenotype of Dedifferentiated Rabbit Chondrocytes by Sesquiterpene Farnesol

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 186
Author(s):  
Guan-Xuan Wu ◽  
Chun-Yu Chen ◽  
Chun-Shien Wu ◽  
Lain-Chyr Hwang ◽  
Shan-Wei Yang ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Prostaglandin E2 ◽  
Proinflammatory Cytokine ◽  
Collagen Synthesis ◽  
Therapeutic Agent ◽  
Interleukin 1Β ◽  
Morphology Change ◽  
Progressive Degeneration ◽  
Joint Disorder ◽  
Inflammatory Effect

Osteoarthritis (OA) is a joint disorder characterized by the progressive degeneration of articular cartilage. The phenotype and metabolism behavior of chondrocytes plays crucial roles in maintaining articular cartilage function. Chondrocytes dedifferentiate and lose their cartilage phenotype after successive subcultures or inflammation and synthesize collagen I and X (COL I and COL X). Farnesol, a sesquiterpene compound, has an anti-inflammatory effect and promotes collagen synthesis. However, its potent restoration effects on differentiated chondrocytes have seldom been evaluated. The presented study investigated farnesol’s effect on phenotype restoration by examining collagen and glycosaminoglycan (GAG) synthesis from dedifferentiated chondrocytes. The results indicated that chondrocytes gradually dedifferentiated through cellular morphology change, reduced expressions of COL II and SOX9, increased the expression of COL X and diminished GAG synthesis during four passages of subcultures. Pure farnesol and hyaluronan-encapsulated farnesol nanoparticles promote COL II synthesis. GAG synthesis significantly increased 2.5-fold after a farnesol treatment of dedifferentiated chondrocytes, indicating the restoration of chondrocyte functions. In addition, farnesol drastically increased the synthesis of COL II (2.5-fold) and GAG (15-fold) on interleukin-1β-induced dedifferentiated chondrocytes. A significant reduction of COL I, COL X and proinflammatory cytokine prostaglandin E2 was observed. In summary, farnesol may serve as a therapeutic agent in OA treatment.

Effects of interleukin-1β on chondroblast viability and extracellular matrix changes in bovine articular cartilage explants

2003 ◽  
Vol 57 (7) ◽  
pp. 314-319 ◽  
Author(s):  
Giordano Stabellini ◽  
Monica De Mattei ◽  
Carla Calastrini ◽  
Nicoletta Gagliano ◽  
Claudia Moscheni ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Cartilage Explants ◽  
Interleukin 1Β ◽  
Bovine Articular Cartilage

scholarly journals miR-200a/b relieves IL-1β-induced cell injury in knee articular chondrocytes ex-vivo by targeting fucosyltransferase 4 (FUT4)

2020 ◽  
Author(s):  
Yintai Li ◽  
Suizhuan Wei ◽  
Zhongping Zhang
Keyword(s):  
Articular Cartilage ◽  
Cell Viability ◽  
Articular Chondrocytes ◽  
Ex Vivo ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Potential Candidate ◽  
Primary Chondrocytes

Abstract Background: Osteoarthritis (OA) is a common subtype of arthritis with prevalence increase with age, and is characterized by the degeneration of articular cartilage. Chondrocytes play curial role in the formation of the articular cartilage. This work aimed to figure out the effect of miR-200a/b in chondrocytes of OA, as well as the underlying molecular mechanism. Methods: Cell viability, apoptosis, pro-inflammatory factors secretion, and matrix degradation were detected with cell counting kit-8 (CCK-8), flow cytometry, enzyme-linked immunosorbent assay (ELISA), and western blotting, separately. Expression of miR-200a/b and fucosyltransferase 4 (FUT4) was measured by RT-qPCR (RNA level) and western blot (protein level). The relationship between miR-200a/b and FUT4 was verified by dual-luciferase assay and RNA immunoprecipitation (RIP) assay. Results: Interleukin 1β (IL-1β) induced OA cell model in primary chondrocytes ex-vivo, as evidenced by cell viability inhibition, apoptosis rate promotion, and IL-6 and tumor necrosis factor α (TNF-α) resection enhancement, as well as Collegen 2a1 (Col2a1) and Aggrecan expression inhibition. Expression of miR-200a/b was downregulated in knee articular cartilage of OA patients and IL-1β-induced primary chondrocytes. miR-200a/b overexpression decreased IL-1β-induced cell injuries, which was further blocked by FUT4 upregulation. Mechanically, FUT4 was negatively regulated by miR-200a/b via target binding. Conclusion: miR-200a/b could alleviate IL-1β-induced chondrocyte injuries via targeting its downstream gene FUT4, suggesting that miR-200a/b-FUT4 axis might be a potential candidate to the treatment of OA.

scholarly journals Developmental Mechanisms in Articular Cartilage Degradation in Osteoarthritis

Arthritis ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Elena V. Tchetina
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Endochondral Ossification ◽  
Cartilage Degradation ◽  
Regulatory Mechanisms ◽  
Disease Development ◽  
Matrix Degradation ◽  
Chondrocyte Phenotype ◽  
Progressive Degeneration ◽  
Developmental Mechanisms

Osteoarthritis is the most common arthritic condition, which involves progressive degeneration of articular cartilage. The most recent accomplishments have significantly advanced our understanding on the mechanisms of the disease development and progression. The most intriguing is the growing evidence indicating that extracellular matrix destruction in osteoarthritic articular cartilage resembles that in the hypertrophic zone of fetal growth plate during endochondral ossification. This suggests common regulatory mechanisms of matrix degradation in OA and in the development and can provide new approaches for the treatment of the disease by targeting reparation of chondrocyte phenotype.

scholarly journals Osteoarthritic Infrapatellar Fat Pad Aggravates Cartilage Degradation via Activation of p38MAPK and ERK1/2 Pathways

2020 ◽  
Author(s):  
Zuoqing Zhou ◽  
Su'an Tang ◽  
Xiaoyu Nie ◽  
Yiqun Zhang ◽  
Delong Li ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Cartilage Degradation ◽  
Cartilage Explants ◽  
Infrapatellar Fat Pad ◽  
Fat Pad ◽  
Primary Chondrocytes ◽  
Tnf Α ◽  
And Cartilage ◽  
Human Primary Chondrocytes

Abstract Background: Although existing studies have suggested the involvement of the infrapatellar fat pad (IPFP) during the development of knee osteoarthritis (OA), the role of IPFP is still controversial. This study aimed to investigate the biochemical effects of osteoarthritic IPFP on cartilage and the underlying mechanisms.Methods: Human IPFP and articular cartilage were collected from end-stage OA patients during total knee arthroplasty. IPFP derived fat-conditioned medium (FCM) was used to stimulate human primary chondrocytes and cartilage explants. CCK8 was used to detect the viability of human chondrocyte. qRT-PCR and western blotting was performed to evaluate the balance of extracellular matrix (ECM) catabolism and anabolism in human chondrocytes with FCM stimulation. Functional effect of osteoarthritic IPFP was also demonstrated in human articular cartilage by ex vivo assay. Activation of relative pathways and its effects on chondrocytes were assessed through immunoblotting and inhibition experiments, respectively. Neutralization test was performed to identify the main factors and their associated pathways responsible for the effects of IPFP. Results: Osteoarthritic IPFP-derived FCM significantly induced extracellular matrix (ECM) degradation in both human primary chondrocytes and cartilage explants. Several pathways, such as NF-κB, mTORC1, p38MAPK, JNK, and ERK1/2 signaling were significantly activated in human chondrocytes with osteoarthritic IPFP-derived FCM stimulation. Interestingly, inhibition of p38MAPK and ERK1/2 signaling pathway could alleviate the detrimental effects of FCM on chondrocytes while inhibition of other signaling pathways had no similar results. In addition, IL-1β and TNF-α instead of IL-6 in osteoarthritic IPFP-derived FCM played a key role in cartilage degradation via activating p38MAPK rather than ERK1/2 signaling pathway.Conclusions: Osteoarthritic IPFP induces the degradation and inflammation of cartilage via activation of p38MAPK and ERK1/2 pathways, in which IL-1β and TNF-α act as the key factors. Our study suggests that modulating the effects of IPFP on cartilage may be a promising strategy for knee OA intervention.

scholarly journals Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2529
Author(s):  
Haeyeop Kim ◽  
Woo Seok Yang ◽  
Khin Myo Htwe ◽  
Mi-Nam Lee ◽  
Young-Dong Kim ◽  
...  
Keyword(s):  
Ethanol Extract ◽  
Serum Levels ◽  
Hepatoprotective Activity ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Related Proteins ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

scholarly journals The stromal vascular fraction mitigates radiation-induced gastrointestinal syndrome in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lydia Bensemmane ◽  
Claire Squiban ◽  
Christelle Demarquay ◽  
Noëlle Mathieu ◽  
Marc Benderitter ◽  
...  
Keyword(s):  
Paneth Cell ◽  
Stromal Vascular Fraction ◽  
Enzymatic Digestion ◽  
Cell Compartment ◽  
Absorption Function ◽  
Radiation Induced ◽  
Anti Inflammatory ◽  
Abdominal Irradiation ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Abstract Background The intestine is particularly sensitive to moderate-high radiation dose and the development of gastrointestinal syndrome (GIS) leads to the rapid loss of intestinal mucosal integrity, resulting in bacterial infiltration, sepsis that comprise patient survival. There is an urgent need for effective and rapid therapeutic countermeasures. The stromal vascular fraction (SVF) derived from adipose tissue is an easily accessible source of cells with angiogenic, anti-inflammatory and regenerative properties. We studied the therapeutic impact of SVF and its action on the intestinal stem cell compartment. Methods Mice exposed to the abdominal radiation (18 Gy) received a single intravenous injection of stromal vascular fraction (SVF) (2.5 × 106 cells), obtained by enzymatic digestion of inguinal fat tissue, on the day of irradiation. Mortality was evaluated as well as intestinal regeneration by histological analyses and absorption function. Results The SVF treatment limited the weight loss of the mice and inhibited the intestinal permeability and mortality after abdominal irradiation. Histological analyses showed that SVF treatment stimulated the regeneration of the epithelium by promoting numerous enlarged hyperproliferative zones. SVF restored CD24+/lysozyme− and Paneth cell populations in the ISC compartment with the presence of Paneth Ki67+ cells. SVF has an anti-inflammatory effect by repressing pro-inflammatory cytokines, increasing M2 macrophages in the ileum and anti-inflammatory monocyte subtypes CD11b+Ly6clowCX3CR1high in the spleen. Conclusions Through the pleiotropic effects that contribute to limiting radiation-induced lethality, SVF opens up attractive prospects for the treatment of emergency GIS.

scholarly journals Anti-Inflammatory Effect of Muscle-Derived Interleukin-6 and Its Involvement in Lipid Metabolism

2021 ◽  
Vol 22 (18) ◽  
pp. 9889
Author(s):  
Hidetoshi Nara ◽  
Rin Watanabe
Keyword(s):  
Lipid Metabolism ◽  
Fatty Liver Disease ◽  
Inflammatory Cytokine ◽  
Suppressive Effect ◽  
Bioactive Substances ◽  
Nonalcoholic Fatty Liver ◽  
Skeletal Muscle Contraction ◽  
The Relationship ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Interleukin (IL)-6 has been studied since its discovery for its role in health and diseases. It is one of the most important pro-inflammatory cytokines. IL-6 was reported as an exacerbating factor in coronavirus disease. In recent years, it has become clear that the function of muscle-derived IL-6 is different from what has been reported so far. Exercise is accompanied by skeletal muscle contraction, during which, several bioactive substances, collectively named myokines, are secreted from the muscles. Many reports have shown that IL-6 is the most abundant myokine. Interestingly, it was indicated that IL-6 plays opposing roles as a myokine and as a pro-inflammatory cytokine. In this review, we discuss why IL-6 has different functions, the signaling mode of hyper-IL-6 via soluble IL-6 receptor (sIL-6R), and the involvement of soluble glycoprotein 130 in the suppressive effect of hyper-IL-6. Furthermore, the involvement of a disintegrin and metalloprotease family molecules in the secretion of sIL-6R is described. One of the functions of muscle-derived IL-6 is lipid metabolism in the liver. However, the differences between the functions of IL-6 as a pro-inflammatory cytokine and the functions of muscle-derived IL-6 are unclear. Although the involvement of myokines in lipid metabolism in adipocytes was previously discussed, little is known about the direct relationship between nonalcoholic fatty liver disease and muscle-derived IL-6. This review is the first to discuss the relationship between the function of IL-6 in diseases and the function of muscle-derived IL-6, focusing on IL-6 signaling and lipid metabolism in the liver.

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