Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes

Ding, Shenglong; Pang, Zhiying; Chen, Xuemei; Li, Zheng; Liu, Xinxin; Zhai, Qilin; Huang, Jian; Ruan, Zhiyong

doi:10.1186/s12950-020-00242-8

Cited by 50 publications

(39 citation statements)

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“…MMP13 is a key enzyme responsible for the degenerative process in cartilage 36 . The inhibition of anabolic factor aggrecan and promotion of catabolic factor MMP13 indicate the degradation of extracellular matrix in cartilage tissues, which contributes to the cartilage injury in OA 37 . In this research, we found that extracellular matrix degradation was indeed caused via IL‐1β, revealed via the reduced aggrecan and increased MMP13.…”

Section: Discussionmentioning

confidence: 58%

CircRNA circ‐IQGAP1 Knockdown Alleviates Interleukin‐1β‐Induced Osteoarthritis Progression via Targeting miR‐671‐5p/TCF4

Peng

Zhang

et al. 2021

Orthopaedic Surgery

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Objective To explore the function of circular RNA IQ motif‐containing GTPase‐activating protein 1 (circ‐IQGAP1) in interleukin (IL)‐1β‐induced osteoarthritis (OA) model and to explore whether circ‐IQGAP1 can modulate microRNA‐671‐5p (miR‐671‐5p) and transcription factor 4 (TCF4) to regulate chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation. Methods The cartilage tissues were collected from 32 OA patients or normal subjects. Human chondrocyte CHON‐001 cells were challenged via different doses of IL‐1β for 24 hours. CHON‐001 cells were transfected with circ‐IQGAP1 overexpression vector, TCF4 overexpression vector, small interfering RNA (siRNA) for circ‐IQGAP1, miR‐671‐5p mimic, miR‐671‐5p inhibitor or corresponding negative controls. Circ‐IQGAP1, miR‐671‐5p and TCF4 abundances in cartilage tissues or CHON‐001 cells were examined via quantitative reverse transcription polymerase chain reaction (qRT‐PCR) or western blot. Cell viability was investigated by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide (MTT). Cell apoptosis was measured by flow cytometry. The inflammatory injury was analyzed by the secretion levels of inflammatory cytokines (IL‐6, IL‐8 and tumor necrosis factor‐α [TNF‐α]) by enzyme‐linked immunosorbent assay (ELISA). The extracellular matrix degradation was evaluated by expression of aggrecan and matrix metalloproteinase 13 (MMP13) via western blot. The target relationship of miR‐671‐5p and circ‐IQGAP1 or TCF4 was analyzed via dual‐luciferase reporter and RNA immunoprecipitation (RIP) analyses. Results Circ‐IQGAP1 abundance was enhanced in the cartilage tissues from OA patients compared with normal subjects (n = 32), and its expression was increased in CHON‐001 cells after treatment of IL‐1β in a dose‐dependent pattern. MiR‐671‐5p expression was decreased in the cartilage tissues from OA patients (n = 32) and IL‐1β‐challenged CHON‐001 cells. MiR‐671‐5p expression was negatively associated with circ‐IQGAP1 level in OA patients. Circ‐IQGAP1 silence mitigated IL‐1β‐caused chondrocyte viability reduction, apoptosis promotion, secretion of inflammatory cytokine (IL‐6, IL‐8 and TNF‐α), and extracellular matrix degradation (reduction of aggrecan and increase of MMP13). MiR‐671‐5p was targeted and inhibited via circ‐IQGAP1. MiR‐671‐5p knockdown attenuated the influence of circ‐IQGAP1 interference on IL‐1β‐caused chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation. TCF4 was targeted via miR‐671‐5p, and TCF4 expression was increased in the cartilage tissues from OA patients (n = 32) and IL‐1β‐challenged CHON‐001 cells. TCF4 abundance in OA patients was negatively correlated with miR‐671‐5p expression. MiR‐671‐5p overexpression alleviated IL‐1β‐mediated chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation via decreasing TCF4 expression. Circ‐IQGAP1 silence reduced TCF4 expression via regulating miR‐671‐5p in IL‐1β‐challenged CHON‐001 cells. Conclusion Circ‐IQGAP1 knockdown attenuated IL‐1β‐caused chondrocyte a...

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Section: Discussionmentioning

confidence: 58%

CircRNA circ‐IQGAP1 Knockdown Alleviates Interleukin‐1β‐Induced Osteoarthritis Progression via Targeting miR‐671‐5p/TCF4

Peng

Zhang

et al. 2021

Orthopaedic Surgery

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“…UroA suppressed pro-inflammatory cytokines, including tumor necrosis factor alpha (TNFα) and interleukin 6 (IL6), decreased nitrite and inducible nitric oxide synthase (iNOS) production, by inhibiting the activation of NFκB signaling pathways [ 28 ]. Consistently, studies reported UroA’s ability to suppress the protein kinase B (Akt)/mitogen-activated protein kinase (MAPK) signaling pathways by either modulating the nuclear translocation of NFκB, inhibiting pro-inflammatory cytokine production, or reducing oxidative stress in various immune cells [ 28 , 29 , 30 , 31 , 32 , 33 ]. In supporting this notion, multiple research studies confirm UroA as a potent mediator to reduce inflammation associated with innate immunity and ROS production, as found in Table 1 .…”

Section: Current Status Of Knowledgementioning

confidence: 95%

Immunomodulatory Role of Urolithin A on Metabolic Diseases

et al. 2021

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Urolithin A (UroA) is a gut metabolite produced from ellagic acid-containing foods such as pomegranates, berries, and walnuts. UroA is of growing interest due to its therapeutic potential for various metabolic diseases based on immunomodulatory properties. Recent advances in UroA research suggest that UroA administration attenuates inflammation in various tissues, including the brain, adipose, heart, and liver tissues, leading to the potential delay or prevention of the onset of Alzheimer’s disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. In this review, we focus on recent updates of the anti-inflammatory function of UroA and summarize the potential mechanisms by which UroA may help attenuate the onset of diseases in a tissue-specific manner. Therefore, this review aims to shed new insights into UroA as a potent anti-inflammatory molecule to prevent immunometabolic diseases, either by dietary intervention with ellagic acid-rich food or by UroA administration as a new pharmaceutical drug.

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“…Results showed that the MAPK and NF- κ B pathways were involved in the protective effects of urolithin A since this metabolite inhibited the phosphorylation of MAPK pathway members thus protecting chondrocytes against IL- β -induced inflammation injury. The overall conclusion of this study was that urolithin A is a promising possible therapeutic agent for the treatment of osteoarthritis [ 48 ]. Importantly, the results of this study confirmed those previously reported by Fu et al [ 49 ].…”

Section: Urolithin Activity In the Modulation Of Oxidative Stressmentioning

confidence: 99%

Ellagic Acid-Derived Urolithins as Modulators of Oxidative Stress

Djedjibegović

Marjanović

Panieri³

et al. 2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress is a state of excess of prooxidative species relative to the antioxidant defenses (enzymatic and nonenzymatic) in a living organism. The consequence of this imbalance is damage of the major cellular macromolecules (carbohydrates, lipids, proteins, and DNA), which further leads to a gradual loss of tissue and organ function. It has been shown that oxidative stress plays an important role in the pathogenesis of many chronic diseases (cardiovascular, metabolic, and neurodegenerative diseases and cancer) and in the process of aging. Thus, many strategies to combat oxidative stress have been proposed and tested. In this context, food rich in antioxidants has received great attention. Pomegranate, berries, and walnuts have been recognized as “superfood” particularly for their cardioprotective effects. The common characteristic of these foods is the high content of ellagitannins. Since tannins are not bioavailable, they have been neglected in nutrition science and even considered antinutrients for a long time. However, this view has changed dramatically once it was recognized that ellagic acid, released from ellagitannins in the gastrointestinal system, is further metabolized by colonic microbiota to bioavailable compounds—known as urolithins. Thus, urolithins (3,4-benzocoumarin derivatives) have emerged as novel natural bioactive compounds and are now the focus of extensive investigations. So far, urolithins were shown to be powerful modulators of oxidative stress and agents with potential anti-inflammatory, antiproliferative, and antiaging properties. Furthermore, a few synthetic derivatives of urolithins were recognized as lead compounds for new drug development. Available data on urolithin synthesis, physicochemical and pharmacokinetic characteristics, biological activity, and safety will be presented in this review.

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Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes

Cited by 50 publications

References 47 publications

CircRNA circ‐IQGAP1 Knockdown Alleviates Interleukin‐1β‐Induced Osteoarthritis Progression via Targeting miR‐671‐5p/TCF4

CircRNA circ‐IQGAP1 Knockdown Alleviates Interleukin‐1β‐Induced Osteoarthritis Progression via Targeting miR‐671‐5p/TCF4

Immunomodulatory Role of Urolithin A on Metabolic Diseases

Ellagic Acid-Derived Urolithins as Modulators of Oxidative Stress

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