The Combination Treatment of Curcumin and Probucol Protects Chondrocytes from TNF‐<i>α</i> Induced Inflammation by Enhancing Autophagy and Reducing Apoptosis via the PI3K‐Akt‐mTOR Pathway

Han, Guoge; Zhang, Yubiao; Li, Haohuan

doi:10.1155/2021/5558066

Cited by 31 publications

(20 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The PI3K/AKT/mTOR signalling pathway is closely related to chondrocyte apoptosis and autophagy 30 . Therefore, PI3K/AKT/mTOR signalling pathway was investigated to further understand the mechanisms through which OI decreases apoptosis and promotes autophagy.…”

Section: Resultsmentioning

confidence: 99%

Four-octyl itaconate improves osteoarthritis by enhancing autophagy in chondrocytes via PI3K/AKT/mTOR signalling pathway inhibition

et al. 2022

View full text Add to dashboard Cite

Osteoarthritis (OA) is a highly prevalent and chronic disorder that is associated with a substantial social and economic burden. Itaconate, as an important regulator of cellular inflammation, is a metabolite synthesised by an enzyme encoded by immune-responsive gene 1. However, there are few studys regarding the effects of itaconate on OA. Here, we show the effect of the cell-permeable itaconate derivative 4-octyl itaconate (OI) on OA. OI attenuates the chondrocyte apoptosis induced by interleukin 1β (IL-1β) in vitro, indicating that OI protect chondrocytes against apoptosis. Moreover, OI ameliorates the chondrocyte autophagy inhibition induced by IL-1β via the inhibition of PI3K/AKT/mTOR signalling pathway. Finally, OI enhances autophagy and reduces cartilage degradation in a rat model of OA established by destabilization of medial meniscus (DMM). In summary, our findings reveal that OI is involved in regulating the progression of OA. The above results shed light on the treatment of OA.

show abstract

Section: Resultsmentioning

confidence: 99%

Four-octyl itaconate improves osteoarthritis by enhancing autophagy in chondrocytes via PI3K/AKT/mTOR signalling pathway inhibition

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The regulatory mechanisms of autophagy are very complex. The PI3K/AKT/mTOR pathway, an essential intracellular signaling pathway, is closely related to chondrocyte apoptosis and autophagy [ 37 ]. Moreover, activation of the PI3K/Akt/mTOR signaling pathway is also critical in the occurrence and development of OA [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Icariin alleviates osteoarthritis through PI3K/Akt/mTOR/ULK1 signaling pathway

et al. 2022

View full text Add to dashboard Cite

Objectives This study aims to investigate the effects of Icariin (ICA) on interleukin-1β (IL-1β)-induced osteoarthritis (OA) and its potential mechanism of action. Methods SW1353 chondrocytes were pretreated with ICA for 2 h, followed by stimulation with IL-1β to mimic OA. Expression levels of matrix metalloproteinases (MMP-3) and collagen II were determined using real-time PCR and Western blot assays. Autophagy activation (by ICA) or inhibition (by shRNA) was determined based on the expression levels of ULK1, Beclin-1, LC3-II/I, and p62, using Western blot analysis. The phosphorylation levels of PI3K, Akt, mTOR, and ULK1 were also detected using Western blot analysis. Results IL-1β increased MMP-3 overproduction, induced collagen II degradation, and reduced the level of autophagy-associated proteins, including ULK1, Beclin-1, and LC3-II/I. In contrast, ICA pretreatment attenuated IL-1β-induced MMP-3 overproduction, increased collagen II expression, and induced expression of autophagy-related proteins. ICA also decreased PI3K, Akt, and mTOR phosphorylation, increased the production of ULK1, and induced autophagy. Short hairpin RNA-mediated knockdown of ULK1 led to activation of the PI3K/Akt/mTOR pathway, which reversed the protective effects of ICA. Conclusions Our findings indicate that ICA can induce autophagy by regulating the PI3K/AKT/mTOR/ULK1 signaling pathway. This study suggests that ICA may be effective for treating OA.

show abstract

“…Another study found that activating PI3K can reduce MMP-13 expression. 52 However, other investigations have shown that specific PI3K and AKT inhibitors can drastically lower MMP expression. 53 These findings highlight the fact that the PI3K/AKT pathway functions as a double-edged sword in ECM metabolism.…”

Section: Discussionmentioning

confidence: 98%

Madecassic Acid Ameliorates the Progression of Osteoarthritis: An in vitro and in vivo Study

Fu¹,

He²,

Wang³

et al. 2022

DDDT

View full text Add to dashboard Cite

Purpose Osteoarthritis (OA) places a significant burden on society and finance, and there is presently no effective treatment besides late replacement surgery and symptomatic relief. The therapy of OA requires additional research. Madecassic acid (MA) is the first native triterpenoid compound extracted from Centella asiatica, which has a variety of anti-inflammatory effects. However, the role of MA in OA therapy has not been reported. This study aimed to explore whether MA could suppress the inflammatory response, preserve and restore chondrocyte functions, and ameliorate the progression of OA in vitro and in vivo. Methods Rat primary chondrocytes were treated with IL-1β to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of MA at concentrations ranging from 0 to 200 µM on the viability of rat chondrocytes and selected 10 µM for further study. Using qRT-PCR, immunofluorescent, immunocytochemistry, and Western blotting techniques, we identified the potential molecular mechanisms and signaling pathways that are responsible for these effects. We established an OA rat model by anterior cruciate ligament transection (ACLT). The animals were then periodically injected with MA into the knee articular cavity. Results We found that MA could down-regulate the IL-1β-induced up-regulation of COX-2, iNOS and IL-6 and restore the cytoskeletal integrity of chondrocytes treated with IL-1β. Moreover, MA protects chondrocytes from IL-1β-induced ECM degradation by upregulating ECM synthesis related protein expression, including collagen-II and ACAN, and further down-regulating ECM catabolic related protein expression, including MMP-3 and MMP-13. Furthermore, we found that NF-κB/IκBα and PI3K/AKT signaling pathways were involved in the regulatory effects of MA on the inflammation inhibition and promotion of ECM anabolism on IL-1β-induced chondrocytes. Conclusion These findings suggest that MA appears to be a potentially small molecular drug for rat OA.

show abstract

The Combination Treatment of Curcumin and Probucol Protects Chondrocytes from TNF‐α Induced Inflammation by Enhancing Autophagy and Reducing Apoptosis via the PI3K‐Akt‐mTOR Pathway

Cited by 31 publications

References 50 publications

Four-octyl itaconate improves osteoarthritis by enhancing autophagy in chondrocytes via PI3K/AKT/mTOR signalling pathway inhibition

Four-octyl itaconate improves osteoarthritis by enhancing autophagy in chondrocytes via PI3K/AKT/mTOR signalling pathway inhibition

Icariin alleviates osteoarthritis through PI3K/Akt/mTOR/ULK1 signaling pathway

Madecassic Acid Ameliorates the Progression of Osteoarthritis: An in vitro and in vivo Study

Contact Info

Product

Resources

About