Effects of simvastatin on matrix metalloproteinase regulation in IL-1β-induced SW1353 cells

Çeçen, Berivan; Keles, Didem; Oktay, Gülgün; Kozacı, Leyla Didem

doi:10.1016/j.cbi.2019.108730

Cited by 7 publications

(5 citation statements)

References 37 publications

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“…As reported previously, statins downregulate MMP3 and ADAMTS5 expressions in chondrosarcoma cells [42] , and our previous studies demonstrated that atorvastatin regulated matrix metabolism in NP cells [22] . In the present study, in vivo experiments verified that rosuvastatin could protect IVDs from degeneration in rat models, and further experiments showed that the induction of the catabolic genes MMP3 and ADAMTS5 by TNF-α was suppressed by rosuvastatin.…”

Section: Discussionsupporting

confidence: 80%

Rosuvastatin suppresses TNF-α-induced matrix catabolism, pyroptosis and senescence via the HMGB1/NF-κB signaling pathway in nucleus pulposus cells

Chen¹,

Deng²,

Zhu³

et al. 2023

ABBS

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Intervertebral disc degeneration is mainly caused by irregular matrix metabolism in nucleus pulposus cells and involves inflammatory factors such as TNF-α. Rosuvastatin, which is widely used in the clinic to reduce cholesterol levels, exerts anti-inflammatory effects, but whether rosuvastatin participates in IDD remains unclear. The current study aims to investigate the regulatory effect of rosuvastatin on IDD and the potential mechanism. In vitro experiments demonstrate that rosuvastatin promotes matrix anabolism and suppresses catabolism in response to TNF-α stimulation. In addition, rosuvastatin inhibits cell pyroptosis and senescence induced by TNF-α. These results demonstrate the therapeutic effect of rosuvastatin on IDD. We further find that HMGB1, a gene closely related to cholesterol metabolism and the inflammatory response, is upregulated in response to TNF-α stimulation. HMGB1 inhibition or knockdown successfully alleviates TNF-α-induced ECM degradation, senescence and pyroptosis. Subsequently, we find that HMGB1 is regulated by rosuvastatin and that its overexpression abrogates the protective effect of rosuvastatin. We then verify that the NF-κB pathway is the underlying pathway regulated by rosuvastatin and HMGB1. In vivo experiments also reveal that rosuvastatin inhibits IDD progression by alleviating pyroptosis and senescence and downregulating HMGB1 and p65. This study might provide new insight into therapeutic strategies for IDD.

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Section: Discussionsupporting

confidence: 80%

Rosuvastatin suppresses TNF-α-induced matrix catabolism, pyroptosis and senescence via the HMGB1/NF-κB signaling pathway in nucleus pulposus cells

Chen¹,

Deng²,

Zhu³

et al. 2023

ABBS

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“…However, serum deprivation could further enhance the susceptibility towards lipopolysaccharides [77] and cytokines, including IL-1β [78], and also induce cell cycle arrest [58], autophagy and apoptosis [79]. In this study, we did not perform the serum deprivation procedure prior to IL-1β treatment, similar to most of the studies on IL-1β-treated SW1353 cells [26,[71][72][73][74].…”

Section: Discussionmentioning

confidence: 97%

“…The proinflammatory cytokine IL-1β was used to induce inflammation in SW1353 chondrocytes at the concentrations of 5-20 ng/mL, but its cytotoxic effect was not determined [61][62][63][64][65][66][67][68][69][70]. Non-cytotoxic effects of IL-1β (5-10 ng/mL) on SW1353 chondrocytes were evident up to 72 h of treatment [26,[71][72][73][74]. Higher (40 ng/mL) or long-term (up to 5 days) treatment of IL-1β also did not affect the viability of SW1353 chondrocytes [73], CHON-002 cells [20] and primary human chondrocytes [75].…”

Section: Discussionmentioning

confidence: 99%

“…Chondrosarcoma cell line SW1353 is one of the most common and established cell lines used as in vitro OA model [15][16][17]23]; its first use in an interleukin (IL)-1-induced inflammation model was recorded in 1987 [24]. To mimic the initiation and pathogenesis of OA, SW1353 chondrocytes are generally stimulated with proinflammatory cytokines like IL-1β or TNF-α to trigger the inflammatory response and catabolic profile, marked by upregulation of MMPs and cytokine production [25,26]. However, IL-1β-stimulated SW1353 cells were reported to express similar but weaker chondrogenic and catabolic profiles compared with primary human chondrocytes [25].…”

Section: Introductionmentioning

confidence: 99%

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Establishing SW1353 Chondrocytes as a Cellular Model of Chondrolysis

Pang

Chow

Leong

et al. 2021

Life

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Osteoarthritis (OA) is the most common degenerative joint disease characterised by chondrocyte cell death. An in vitro model of chondrocyte cell death may facilitate drug discovery in OA management. In this study, the cytotoxicity and mode of cell death of SW1353 chondrocytes treated with 24 h of OA inducers, including interleukin-1β (IL-1β), hydrogen peroxide (H2O2) and monosodium iodoacetate (MIA), were investigated. The microscopic features, oxidative (isoprostane) and inflammatory markers (tumour necrosis factor-alpha; TNF-α) for control and treated cells were compared. Our results showed that 24 h of H2O2 and MIA caused oxidative stress and a concentration-dependent reduction of SW1353 cell viability without TNF-α level upregulation. H2O2 primarily induced chondrocyte apoptosis with the detection of blebbing formation, cell shrinkage and cellular debris. MIA induced S-phase arrest on chondrocytes with a reduced number of attached cells but without significant cell death. On the other hand, 24 h of IL-1β did not affect the cell morphology and viability of SW1353 cells, with a significant increase in intracellular TNF-α levels without inducing oxidative stress. In conclusion, each OA inducer exerts differential effects on SW1353 chondrocyte cell fate. IL-1β is suitable in the inflammatory study but not for chondrocyte cell death. H2O2 and MIA are suitable for inducing chondrocyte cell death and growth arrest, respectively.

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“…Furthermore, the aberrant activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase (HMGCR), the rate-limiting enzyme of MVA pathway, can promote malignant transformation (7) and provides essential metabolites (i.e., sterols and non-sterol intermediates) that collectively drive tumor growth and development. Despite clinical evidences supporting the use of MVA pathway inhibitors (i.e., statins) for limiting cancer morbimortality are relatively low, increasing preclinical (11)(12)(13)(14)(15)(16)(17)(18)(19) and epidemiological (20)(21)(22)(23)(24)(25)(26)(27)(28) studies sustain the inverse association between statins and cancer-specific mortality rate. This beneficial effects of statins have been described in several types of cancer, including osteosarsocoma/chondrosarcoma (16)(17)(18), prostate (24,26), colon (29,30), breast (19,31), liver (32,33), pancreas (34), ovarian (35,36), esophageal (37,38), lung (39), and hematological malignances (40).…”

Section: Introductionmentioning

confidence: 99%

The Mevalonate Pathway, a Metabolic Target in Cancer Therapy

et al. 2021

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A hallmark of cancer cells includes a metabolic reprograming that provides energy, the essential building blocks, and signaling required to maintain survival, rapid growth, metastasis, and drug resistance of many cancers. The influence of tumor microenviroment on cancer cells also results an essential driving force for cancer progression and drug resistance. Lipid-related enzymes, lipid-derived metabolites and/or signaling pathways linked to critical regulators of lipid metabolism can influence gene expression and chromatin remodeling, cellular differentiation, stress response pathways, or tumor microenviroment, and, collectively, drive tumor development. Reprograming of lipid metabolism includes a deregulated activity of mevalonate (MVA)/cholesterol biosynthetic pathway in specific cancer cells which, in comparison with normal cell counterparts, are dependent of the continuous availability of MVA/cholesterol-derived metabolites (i.e., sterols and non-sterol intermediates) for tumor development. Accordingly, there are increasing amount of data, from preclinical and epidemiological studies, that support an inverse association between the use of statins, potent inhibitors of MVA biosynthetic pathway, and mortality rate in specific cancers (e.g., colon, prostate, liver, breast, hematological malignances). In contrast, despite the tolerance and therapeutic efficacy shown by statins in cardiovascular disease, cancer treatment demands the use of relatively high doses of single statins for a prolonged period, thereby limiting this therapeutic strategy due to adverse effects. Clinically relevant, synergistic effects of tolerable doses of statins with conventional chemotherapy might enhance efficacy with lower doses of each drug and, probably, reduce adverse effects and resistance. In spite of that, clinical trials to identify combinatory therapies that improve therapeutic window are still a challenge. In the present review, we revisit molecular evidences showing that deregulated activity of MVA biosynthetic pathway has an essential role in oncogenesis and drug resistance, and the potential use of MVA pathway inhibitors to improve therapeutic window in cancer.

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Effects of simvastatin on matrix metalloproteinase regulation in IL-1β-induced SW1353 cells

Cited by 7 publications

References 37 publications

Rosuvastatin suppresses TNF-α-induced matrix catabolism, pyroptosis and senescence via the HMGB1/NF-κB signaling pathway in nucleus pulposus cells

Rosuvastatin suppresses TNF-α-induced matrix catabolism, pyroptosis and senescence via the HMGB1/NF-κB signaling pathway in nucleus pulposus cells

Establishing SW1353 Chondrocytes as a Cellular Model of Chondrolysis

The Mevalonate Pathway, a Metabolic Target in Cancer Therapy

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Effects of simvastatin on matrix metalloproteinase regulation in IL-1β-induced SW1353 cells

Cited by 7 publications

References 37 publications

Rosuvastatin suppresses TNF-&alpha;-induced matrix catabolism, pyroptosis and senescence via the HMGB1/NF-&kappa;B signaling pathway in nucleus pulposus cells

Rosuvastatin suppresses TNF-&alpha;-induced matrix catabolism, pyroptosis and senescence via the HMGB1/NF-&kappa;B signaling pathway in nucleus pulposus cells

Establishing SW1353 Chondrocytes as a Cellular Model of Chondrolysis

The Mevalonate Pathway, a Metabolic Target in Cancer Therapy

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Product

Resources

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Rosuvastatin suppresses TNF-α-induced matrix catabolism, pyroptosis and senescence via the HMGB1/NF-κB signaling pathway in nucleus pulposus cells

Rosuvastatin suppresses TNF-α-induced matrix catabolism, pyroptosis and senescence via the HMGB1/NF-κB signaling pathway in nucleus pulposus cells