The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis

Sellam, Jérémie; Bérenbaum, Francis

doi:10.1038/nrrheum.2010.159

Cited by 1,163 publications

(1,033 citation statements)

References 97 publications

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“…Several studies have thereafter supported a shift to the concept that inflammation is central to disease progression in both early and late osteoarthritis (38). As to degradation, members of the MMP family, active in breakdown of extracellular matrix in both physiological and pathological processes (39), along with proinflammatory genes are induced via the NF-kB pathway in osteoarthritic chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

Galectin-1 Couples Glycobiology to Inflammation in Osteoarthritis through the Activation of an NF-κB–Regulated Gene Network

Toegel

Weinmann

André

et al. 2016

The Journal of Immunology

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Osteoarthritis is a degenerative joint disease that ranks among the leading causes of adult disability. Mechanisms underlying osteoarthritis pathogenesis are not yet fully elucidated, putting limits to current disease management and treatment. Based on the phenomenological evidence for dysregulation within the glycome of chondrocytes and the network of a family of adhesion/growth-regulatory lectins, that is, galectins, we tested the hypothesis that Galectin-1 is relevant for causing degeneration. Immunohistochemical analysis substantiated that Galectin-1 upregulation is associated with osteoarthritic cartilage and subchondral bone histopathology and severity of degeneration (p < 0.0001, n = 29 patients). In vitro, the lectin was secreted and it bound to osteoarthritic chondrocytes inhibitable by cognate sugar. Glycan-dependent Galectin-1 binding induced a set of disease markers, including matrix metalloproteinases and activated NF-κB, hereby switching on an inflammatory gene signature (p < 10−16). Inhibition of distinct components of the NF-κB pathway using dedicated inhibitors led to dose-dependent impairment of Galectin-1–mediated transcriptional activation. Enhanced secretion of effectors of degeneration such as three matrix metalloproteinases underscores the data’s pathophysiological relevance. This study thus identifies Galectin-1 as a master regulator of clinically relevant inflammatory-response genes, working via NF-κB. Because inflammation is critical to cartilage degeneration in osteoarthritis, this report reveals an intimate relation of glycobiology to osteoarthritic cartilage degeneration.

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Section: Discussionmentioning

confidence: 99%

Galectin-1 Couples Glycobiology to Inflammation in Osteoarthritis through the Activation of an NF-κB–Regulated Gene Network

Toegel

Weinmann

André

et al. 2016

The Journal of Immunology

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“…Over the years, there has been strong evidence that in OA, TNF-α is one of the most important mediators which alters the balance of cartilage matrix degradation and repair, leading finally to cartilage breakdown [12].…”

Section: Discussionmentioning

confidence: 99%

Association analysis of two candidate polymorphisms in the Tumour Necrosis Factor-α gene with osteoarthritis in a Chinese population

Shi

Cheng

et al. 2013

International Orthopaedics (SICOT)

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Purpose The purpose of this study was to investigate the possible association between single nucleotide polymorphisms (SNPs) rs1800629 (TNF-α -308) and rs361525 (TNF-α -238) of the tumour necrosis factor (TNF)-α gene and susceptibility to osteoarthritis (OA) in the Han Chinese population. Methods The TNF-α -308 and -238 genotypes were determined by TaqMan assay in 200 OA cases and 305 controls. Odds ratios (ORs) for OA and 95 % confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks. Results The frequencies of the allele 'A' of rs1800629 were 16 % and 8.85 % in OA cases and in controls, respectively, and thus the -308A allele had a 1.9612-fold (95 % CI=1.3323-2.8869, P<0.001) increased risk for OA as compared to the -308G allele. However, no significant differences were found in the genotype and allele frequencies for rs361525 between OA and HC groups. Conclusions In the Han Chinese population, the allele 'A' of TNF-α -308 may increase the risk for OA, whereas TNF-α -238 polymorphisms do not play a role in OA patients.

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“…33 Since SDSCs are used to facilitate cartilage tissue regeneration, it is critical to consider the effect of synovitis on chondrogenic differentiation of OA SDSCs since inflammatory cytokines have previously been shown to inhibit chondrogenesis. 27,28 CD14 is a glycoprotein expressed on the surface of myelomonocytic cells as a GPI-anchored receptor or secreted in a soluble form.…”

Section: Cd14 and Proinflammatory Cytokines On Chondrogenesis In Oa Smentioning

confidence: 99%

Effects of CD14 Macrophages and Proinflammatory Cytokines on Chondrogenesis in Osteoarthritic Synovium-Derived Stem Cells

Sun

Lee

Seong

et al. 2014

Tissue Engineering Part A

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We investigated the effects of CD14 macrophages and proinflammatory cytokines on chondrogenic differentiation of osteoarthritic synovium-derived stem cells (SDSCs). Osteoarthritic synovial fluid was analyzed for interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), and IL-6. Levels of stem cell surface markers in osteoarthritic SDSCs were evaluated using flow cytometry. CD14-negative cells were obtained using magnetically activated cell sorting. We compared chondrogenic potentials between whole cells and CD14-negative cells in CD14 low cells and CD14 high cells, respectively. To assess whether nuclear factor-kB (NF-kB) and CCAAT/enhancer-binding protein b (C/EBPb) modulate IL-1b-induced alterations in chondrogenic potential, we performed small interfering RNA transfection. We observed a significant correlation between the CD14 ratio in osteoarthritic SDSCs and IL-1b and TNF-a in osteoarthritic synovial fluid. Phenotypic characterization of whole cells and CD14-negative cells showed no significant differences in levels of stem cell markers. mRNA expression of type II collagen was higher in CD14-negative cell pellets than in whole cell pellets. Immunohistochemical staining indicated higher levels of type II collagen in the CD14-negative cell pellets of CD14 high cells than in whole cell pellets of CD14 high cells. As expected, IL-1b and TNF-a significantly inhibited the expression of chondrogenic-related genes in SDSCs, an effect which was antagonized by knockdown of NF-kB and C/EBPb. Our results suggest that depletion of CD14 + synovial macrophages leads to improved chondrogenic potential in CD14 high cell populations in osteoarthritic SDSCs, and that NF-kB (RelA) and C/EBPb are critical factors mediating IL-1b-induced suppression of the chondrogenic potential of human SDSCs.

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The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis

Cited by 1,163 publications

References 97 publications

Galectin-1 Couples Glycobiology to Inflammation in Osteoarthritis through the Activation of an NF-κB–Regulated Gene Network

Galectin-1 Couples Glycobiology to Inflammation in Osteoarthritis through the Activation of an NF-κB–Regulated Gene Network

Association analysis of two candidate polymorphisms in the Tumour Necrosis Factor-α gene with osteoarthritis in a Chinese population

Effects of CD14 Macrophages and Proinflammatory Cytokines on Chondrogenesis in Osteoarthritic Synovium-Derived Stem Cells

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