The autophagic response to oxidative stress in osteoarthritic chondrocytes is deregulated

Goutas, Andreas; Syrrou, Christina; Papathanasiou, Ioanna V.; Tsezou, Aspasia; Trachana, Varvara

doi:10.1016/j.freeradbiomed.2018.08.003

Cited by 39 publications

(50 citation statements)

References 61 publications

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“…21 It was also shown that enhanced autophagy is linked to consumption of excessive ROS and thus protection of chondrocytes. 22 Quantitative RT-PCR analysis showed that IL-1β led to a marginal increase of specific autophagy markers, including LC3-Ⅱ, ATG7 and Beclin-1, compared with normal chondrocytes. By contrast, DM nanoparticles drastically elevated the expression of these autophagy markers in IL-1β-pretreated chondrocytes (Figure 5f).…”

Section: Dm Nanoparticles Stimulate Autophagy For Chondrocyte Protectionmentioning

confidence: 98%

Dopamine-melanin nanoparticles scavenge reactive oxygen and nitrogen species and activate autophagy for osteoarthritis therapy

et al. 2019

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Section: Dm Nanoparticles Stimulate Autophagy For Chondrocyte Protectionmentioning

confidence: 98%

Dopamine-melanin nanoparticles scavenge reactive oxygen and nitrogen species and activate autophagy for osteoarthritis therapy

et al. 2019

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“…Autophagy disturbances are frequently caused by these mechanisms: inhibition of autophagy initiation, interruption of autophagosome-lysosome fusion, and damage to lysosomal function [12]. Moreover, autophagy dysfunction has been widely reported to be closely related to cell senescence and apoptosis in the progression of several diseases, particularly degenerative diseases such as osteoarthritis [13], IDD [14], neurodegenerative disorders [15], and age-related macular degeneration [16]. Notably, Xu et al found that treatment of rat NP cells with rapamycin (Rap), a classical autophagy activator, can potently prevent ECM degradation induced by inflammatory factors such as tumor necrosis factor-α and interleukin-1β [17].…”

Section: Introductionmentioning

confidence: 99%

Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration

Kang

Xiang

Zhan

et al. 2019

Oxidative Medicine and Cellular Longevity

107

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Oxidative stress-induced mitochondrial dysfunction and nucleus pulposus (NP) cell apoptosis play crucial roles in the development of intervertebral disc degeneration (IDD). Increasing studies have shown that interventions targeting impaired autophagic flux can maintain cellular homeostasis by relieving oxidative damage. Here, we investigated the effect of curcumin (CUR), a known autophagy activator, on IDD in vitro and in vivo. CUR suppressed tert-butyl hydroperoxide- (TBHP-) induced oxidative stress and mitochondrial dysfunction and thereby inhibited human NP cell apoptosis, senescence, and ECM degradation. CUR treatment induced autophagy and enhanced autophagic flux in an AMPK/mTOR/ULK1-dependent manner. Notably, CUR alleviated TBHP-induced interruption of autophagosome-lysosome fusion and impairment of lysosomal function and thus contributed to the restoration of blocked autophagic clearance. These protective effects of CUR in TBHP-stimulated human NP cells resembled the effects produced by the autophagy inducer rapamycin, but the effects were partially eliminated by 3-methyladenine- and compound C-mediated inhibition of autophagy initiation or chloroquine-mediated obstruction of autophagic flux. Lastly, CUR also exerted a protective effect against puncture-induced IDD progression in vivo. Our results showed that suppression of excessive ROS production and mitochondrial dysfunction through enhancement of autophagy coupled with restoration of autophagic flux ameliorated TBHP-induced human NP cell apoptosis, senescence, and ECM degradation. Thus, maintenance of the proper functioning of autophagy represents a promising therapeutic strategy for IDD, and CUR might serve as an effective therapeutic agent for IDD.

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“…Much work has been devoted to the search of a safe and effective mean to rescue autophagy. Recent research has suggested that the downregulated autophagy of OA compared to healthy chondrocytes derives from an altered kinetic pattern of the process as indicated by the different behavior of pivotal autophagic proteins after an oxidative challenge [5]. Rescue of an efficient autophagic flux could therefore at the same time improve clearance of damaged molecules, cell homeostasis and viability.…”

Section: Introductionmentioning

confidence: 99%

“…Chondrocyte susceptibility to OS markedly changes as a function of the culture density and exposure length [17]. Compared to a previous report [5] we chose an H 2 O 2 exposure (dose/time) beyond the threshold of cell death to fully assess SPD chondroprotective activity. Exposure to OS is responsible for multiple cell features such as oxidative damage to mitochondria and genomic DNA.…”

Section: Introductionmentioning

confidence: 99%

Spermidine rescues the deregulated autophagic response to oxidative stress of osteoarthritic chondrocytes

D’Adamo

Cetrullo

Guidotti

et al. 2020

Free Radical Biology and Medicine

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Oxidative stress (OS) contributes to Osteoarthritis (OA) pathogenesis and its effects are worsened by the impairment of homeostatic mechanisms such as autophagy in OA chondrocytes. Rescue of an efficient autophagic flux could therefore reduce the bulk of damaged molecules, and at the same time improve cell function and viability. As a promising dietary or intra-articular supplement to rescue autophagy in OA chondrocytes, we tested spermidine (SPD), known to induce autophagy and to reduce OS in several other cellular models. Chondrocytes were obtained from OA cartilage and seeded at high-density to keep their differentiated phenotype. The damaging effects of OS and the chondroprotective activity of SPD were assessed by evaluating the extent of cell death, oxidative DNA damage and caspase 3 activation. The autophagy promoting activity of SPD was evaluated by assessing pivotal autophagic effectors, i.e. Beclin-1 (BECN-1), microtubule-associated protein 1 light chain 3 II (LC3-II) and p62. BECN-1 protein expression was significantly increased by SPD and reduced by H 2 O 2 treatment. SPD also rescued the impaired autophagic flux consequent to H 2 O 2 exposure by increasing mRNA and protein expression of LC3-II and p62. SPD induction of mitophagy was revealed by immunofluorescent co-localization of LC3-II and TOM20. The key protective role of autophagy was confirmed by the loss of SPD chondroprotection upon autophagy-related gene 5 (ATG5) silencing. Significant SPD tuning of the H 2 O 2-dependent induction of degradative (MMP-13) inflammatory (iNOS, COX-2) and hypertrophy markers (RUNX2 and VEGF) was revealed by Real Time PCR and pointed at the SPD ability of reducing NF-κB activation through autophagy induction. Conversely, blockage of autophagy led to parallel increases of oxidative markers and p65 nuclear translocation. SPD also increased the proliferation of slow-proliferating primary cultures.Taken together, our findings highlight the chondroprotective, anti-oxidant and anti-inflammatory activity of SPD and suggest that the protection afforded by SPD against OS is exerted through the rescue of the autophagic flux.

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The autophagic response to oxidative stress in osteoarthritic chondrocytes is deregulated

Cited by 39 publications

References 61 publications

Dopamine-melanin nanoparticles scavenge reactive oxygen and nitrogen species and activate autophagy for osteoarthritis therapy

Dopamine-melanin nanoparticles scavenge reactive oxygen and nitrogen species and activate autophagy for osteoarthritis therapy

Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration

Spermidine rescues the deregulated autophagic response to oxidative stress of osteoarthritic chondrocytes

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