Chondroitin Sulfate Inhibits the Nuclear Translocation of Nuclear Factor‐κB in Interleukin‐1β‐Stimulated Chondrocytes

Jomphe, Claudia; Gabriac, Mélanie; Hale, Taben M.; Héroux, Lucie; Trudeau, Louis-Éric; deBlois, Denis; Montell, E.; Vergés, Josep; Souich, Patrick du

doi:10.1111/j.1742-7843.2007.00158.x

Cited by 107 publications

(78 citation statements)

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“…As a result, NF-B binds to target genes, increasing the expression of many OA-related proteins, such as pro-inflammatory cytokines (IL-1␤, IL-6, and TNF-␣) and matrix metalloproteases (MMPs) (33). In chondrocyte cultures, it has been shown that bovine CS diminishes IL-1␤-induced NF-B nuclear translocation (43), although the mechanism for this reduction remains unclear. Our data suggest that the anti-inflammatory activity of CS might be related to its effect on the proteasome.…”

Section: Discussionmentioning

confidence: 99%

Pharmacoproteomic Study of Three Different Chondroitin Sulfate Compounds on Intracellular and Extracellular Human Chondrocyte Proteomes

Calamia

Fernández-Puente

Mateos

et al. 2012

Molecular & Cellular Proteomics

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Chondroitin sulfate (CS) is a symptomatic slow acting drug for osteoarthritis (OA) widely used for the treatment of this highly prevalent disease, characterized by articular cartilage degradation. However, little is known about its mechanism of action, and recent large scale clinical trials have reported variable results on OA symptoms. Herein, we aimed to study the modulations in the intracellular proteome and the secretome of human articular cartilage cells (chondrocytes) treated with three different CS compounds, with different origin or purity, by two complementary proteomic approaches. Osteoarthritic cells were treated with 200 g/ml of each brand of CS. Quantitative proteomics experiments were carried out by the DIGE and stable isotope labeling with amino acids in cell culture (SILAC) techniques, followed by LC-MALDI-MS/MS analysis. The DIGE study, carried out on chondrocyte whole cell extracts, led to the detection of 46 spots that were differential between conditions in our study: 27 were modulated by CS1, 4 were modulated by CS2, and 15 were modulated by CS3. The SILAC experiment, carried out on the subset of chondrocyte-secreted proteins, allowed us to identify 104 different proteins. Most of them were extracellular matrix components, and 21 were modulated by CS1, 13 were modulated by CS2, and 9 were modulated by CS3. Each of the studied compounds induces a characteristic protein profile in OA chondrocytes. CS1 displayed the widest effect but increased the mitochondrial superoxide dismutase, the cartilage oligomeric matrix protein, and some catabolic or inflammatory factors like interstitial collagenase, stromelysin-1, and pentraxin-related protein. CS2 and CS3, on the other hand, increased a number of structural proteins, growth factors, and extracellular matrix proteins. Our study shows how, from the three CS compounds tested, CS1 induces the activation of inflammatory and catabolic pathways, whereas CS2 and CS3 induce an anti-inflammatory and anabolic response. The data presented emphasize the importance of employing high quality CS compounds, supported by controlled clinical trials, in the therapy of OA. Finally, the present work exemplifies the usefulness of proteomic approaches in pharmacological studies. Molecular & Cellular Proteomics

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Section: Discussionmentioning

confidence: 99%

Pharmacoproteomic Study of Three Different Chondroitin Sulfate Compounds on Intracellular and Extracellular Human Chondrocyte Proteomes

Calamia

Fernández-Puente

Mateos

et al. 2012

Molecular & Cellular Proteomics

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“…Preincubation with soluble heparin and chondroitin sulphate has previously been shown to dampen the inflammatory response in cells stimulated with IL-1β, correlated with reduced NF-κB signalling, but the mechanisms of action by the polysaccharides are not clear (Hochart et al, 2006;Jomphe et. al., 2008;Legendre et al, 2008).…”

Section: ø Arlov Et Al Biomimetic Sulphated Alginate Hydrogelsmentioning

confidence: 99%

Biomimetic sulphated alginate hydrogels suppress IL-1β-induced inflammatory responses in human chondrocytes

Arlov¹,

Öztürk²,

Steinwachs³

et al. 2017

eCM

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Loss of articular cartilage from ageing, injury or degenerative disease is commonly associated with inflammation, causing pain and accelerating degradation of the cartilage matrix. Sulphated glycosaminoglycans (GAGs) are involved in the regulation of immune responses in vivo, and analogous polysaccharides are currently being evaluated for tissue engineering matrices to form a biomimetic environment promoting tissue growth while suppressing inflammatory and catabolic activities. Here, we characterise physical properties of sulphated alginate (S-Alg) gels for use in cartilage engineering scaffolds, and study their anti-inflammatory effects on encapsulated chondrocytes stimulated with IL-1β. Sulphation resulted in decreased storage modulus and increased swelling of alginate gels, whereas mixing highly sulphated alginate with unmodified alginate resulted in improved mechanical properties compared to gels from pure S-Alg. S-Alg gels showed extensive anti-inflammatory and anti-catabolic effects on encapsulated chondrocytes induced by IL-1β. Cytokine-stimulated gene expression of pro-inflammatory markers IL-6, IL-8, COX-2 and aggrecanase ADAMTS-5 were significantly lower in the sulphated gels compared to unmodified alginate gels. Moreover, sulphation of the microenvironment suppressed the protein expression of COX-2 and NF-κB as well as the activation of NF-κB and p38-MAPK. The sulphated alginate matrices were found to interact with IL-1β, and proposed to inhibit inflammatory induction by sequestering cytokines from their receptors. This study shows promising potential for sulphated alginates in biomimetic tissue engineering scaffolds, by reducing cytokine-mediated inflammation and providing a protective microenvironment for encapsulated cells.

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“…По-видимому, некоторые различия в механиз-мах действия ХС и ГА могут объяснить более выраженную эффективность их комбинации по сравнению с монопре-паратами [9][10][11]. Синергичный эффект ХС и ГА подтверж-ден в различных in vivo и in vitro исследованиях.…”

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Use of Drugs Arthra MSM Forte and Arthra for Osteoarthritis and Back Pains

Алексеева¹,

Шарапова²

2017

Med. sov.

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Боль -наиболее частый симптом, который является причиной обращения больного к врачу, при этом ведущее место занимают боли в нижней части спины (БНС) и суставах. На сегодняшний день лечение ОА и БНС направлено в первую очередь на симптомы болезни, т. е. на уменьшение болевого синдрома и улучшение функционального состояния суставов и позвоночника. Применение НПВП позволяет быстро снизить интенсивность боли и ускорить восстановление двигатель-ной активности при ОА и БНС. Однако применение этой группы препаратов связано с развитием нежелательных явлений со стороны желудочно-кишечного тракта, сердечно-сосудистой системы, почек и других органов, что особенно важно при коморбидных состояниях у пожилых больных. В связи с этим становится понятным высокий интерес к группе препаратов с замедленным симптоматическим действием, которые превосходно зарекомендовали себя в артрологической практике. К этой группе относятся глюкозамин (ГА), хондроитин сульфат (ХС), которые имеют наиболее высокую доказательную базу по эффективности. В многочисленных клинических исследованиях было показано, что ХС и ГА обладают противовоспали-тельными свойствами, что способствует уменьшению болевого синдрома и может быть полезным при лечении ОА и БНС.Ключевые слова: остеоартроз, болевой синдром, клиническая эффективность, переносимость, нежелательные явления. L.I. ALEKSEEVA, MD, Prof., E.P. SHARAPOVA,, PhD in medicine V.A. Nasonova Research Institute of Rheumatology, Moscow USE OF DRUGS ARTHRA MSM FORTE AND ARTHRA FOR OSTEOARTHRITIS AND BACK PAINSPain is the most common symptom that causes the patient to contact a doctor, and the lower back and joints are the major places where it occurs. To date treatment of OA and lower back pain (LBP) is focused primarily on the symptoms of disease, that is, reducing pain syndrome and improving the functional state of joints and spine. The use of NSAIDs can quickly reduce the intensity of pain and accelerate the recovery of the motor activity in OA and LBP. However, the use of this group of drugs is related to the development of undesirable events on the part of the gastrointestinal tract, cardiovascular system, kidneys and other organs, which is particularly important in the comorbid conditions of the elderly patients. This makes it clear that there is a high level of interest in the slow-symptomatic drug group that approved themselves in the arthrologic practice. This group includes glucosamine (GA), chondroitin sulphate (CS), which have the highest evidentiary basis by efficiency. Numerous clinical studies have shown that CS and GA have anti-inflammatory characteristics contributing to reducing pain syndrome and can be useful in treating OA and LBP.

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Chondroitin Sulfate Inhibits the Nuclear Translocation of Nuclear Factor‐κB in Interleukin‐1β‐Stimulated Chondrocytes

Cited by 107 publications

References 46 publications

Pharmacoproteomic Study of Three Different Chondroitin Sulfate Compounds on Intracellular and Extracellular Human Chondrocyte Proteomes

Pharmacoproteomic Study of Three Different Chondroitin Sulfate Compounds on Intracellular and Extracellular Human Chondrocyte Proteomes

Biomimetic sulphated alginate hydrogels suppress IL-1β-induced inflammatory responses in human chondrocytes

Use of Drugs Arthra MSM Forte and Arthra for Osteoarthritis and Back Pains

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