Increased expression of lipocalin-type prostaglandin D<Subscript>2</Subscript>synthase in osteoarthritic cartilage

Introduction  

Prostaglandin D synthase (PGDS) is responsible for the biosynthesis of PGD and J series, which have been shown to exhibit anti-inflammatory and anticatabolic effects. Two isoforms have been identified: hematopoietic- and lipocalin-type PGDS (H-PGDS and L-PGDS, respectively). The aims of this study were to investigate the expressions of H-PGDS and L-PGDS in cartilage from healthy donors and from patients with osteoarthritis (OA) and to characterize their regulation by interleukin-1-beta (IL-1β) in cultured OA chondrocytes.     

High mobility group box 1 potentiates the pro-inflammatory effects of interleukin-1β in osteoarthritic synoviocytes

Introduction  

High mobility group box 1 (HMGB1) is released by necrotic cells or secreted in response to inflammatory stimuli. Extracellular HMGB1 may act as a pro-inflammatory cytokine in rheumatoid arthritis. We have recently reported that HMGB1 is released by osteoarthritic synoviocytes after activation with interleukin-1beta (IL-1β) The present study investigated the role of HMGB1 in synovial inflammation in osteoarthritis (OA).     

Iterleukin 1 alpha is a marker of endothelial cellular senescent

Background  

The functional changes associated with endothelial senescence may be involved in human aging and age-related vascular disorders. Since the inflammatory cytokine interleukin (IL-)1 inhibits endothelial growth, we evaluated the expression of IL-1α, IL-1β and their antagonist, the IL-1 receptor antagonist (IL-1ra), in endothelial in vitro senescence and quiescence. We also examined the expression of IL-1α in human senescent and progeric fibroblasts.     

Regulation of catabolic gene expression in normal and degenerate human intervertebral disc cells: implications for the pathogenesis of intervertebral disc degeneration

Introduction  

The aim of this study was to compare the effects of tumour necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β) on protease and catabolic cytokine and receptor gene expression in normal and degenerate human nucleus pulposus cells in alginate culture.     

Innate immunity triggers IL-32 expression by fibroblast-like synoviocytes in rheumatoid arthritis

Introduction  

Interleukin-32 (IL-32) is a recently described cytokine that is a strong inducer of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, IL-1β, IL-6, and IL-8. The expression of this cytokine is highly increased in the rheumatoid synovium and correlated with the severity of joint inflammation. Little is known regarding the innate immune-related regulation of IL-32 by fibroblast-like synoviocytes (FLSs). We therefore investigated the effect of innate immune stimulation by ligands of Toll-like receptor (TLR)2, TLR3, and TLR4, and cytokines such as TNF-α and interferon (IFN)-γ, on IL-32 expression by FLSs.     

Retinoid X receptor and peroxisome proliferator-activated receptor-gamma agonists cooperate to inhibit matrix metalloproteinase gene expression

Introduction  

We recently described the ability of retinoid X receptor (RXR) ligand LG100268 (LG268) to inhibit interleukin-1-beta (IL-1-β)-driven matrix metalloproteinase-1 (MMP-1) and MMP-13 gene expression in SW-1353 chondrosarcoma cells. Other investigators have demonstrated similar effects in chondrocytes treated with rosiglitazone, a ligand for peroxisome proliferator-activated receptor-gamma (PPARγ), for which RXR is an obligate dimerization partner. The goals of this study were to evaluate the inhibition of IL-1-β-induced expression of MMP-1 and MMP-13 by combinatorial treatment with RXR and PPARγ ligands and to investigate the molecular mechanisms of this inhibition.     

Polyoxypregnane glycoside from Dregea volubilis extract inhibits IL-1β-induced expression of matrix metalloproteinase via activation of NF-κB in human chondrocytes

Interleukin-1β (IL-1β) induces the expression of matrix metalloproteinases (MMPs) implicated in cartilage and joint degradation in osteoarthritis (OA) and rheumatoid arthritis (RA). Polyoxypregnane glycoside (PPG), active compound was identified from Dregea volubilis extract by chemical analysis, shown to exert chondroprotective effects in cartilage explant models. However, no studies have been undertaken for the molecular investigation of whether PPG constituents protect the human articular chondrocyte (HAC). In the present studies, HAC was co-treated with IL-1β and PPG. The expression of MMPs, type II collagen, phosphorylation of mitogen-activated protein kinases (MAPKs) and NF-κB signaling pathway were determined by Western immunoblotting. PPG (6.25–25 μM) decreased the IL-1β-induced HA release from chondrocyte to culture medium. The mode of action of PPG was likely mediated through inhibiting expression of MMP-1, -3 and -13 in the medium, which was associated with the inhibition of mRNA expression. PPG had no effect on IL-1β-induced phosphorylation of MAPK pathway. Conversely, PPG decreased phosphorylation of IκB kinase and IκBα degradation. Taken together, these results indicate that PPG may inhibit cartilage degradation in OA and may also be used as nutritional supplement for maintaining joint integrity and function.     

Effect of interleukin-1β on spinal cord nociceptive transmission of normal and monoarthritic rats after disruption of glial function

Introduction  

Cytokines produced by spinal cord glia after peripheral injuries have a relevant role in the maintenance of pain states. Thus, while IL-1β is overexpressed in the spinal cords of animals submitted to experimental arthritis and other chronic pain models, intrathecal administration of IL-1β to healthy animals induces hyperalgesia and allodynia and enhances wind-up activity in dorsal horn neurons.     

Green tea polyphenol epigallocatechin-3-gallate inhibits advanced glycation end product-induced expression of tumor necrosis factor-α and matrix metalloproteinase-13 in human chondrocytes

Introduction  

The major risk factor for osteoarthritis (OA) is aging, but the mechanisms underlying this risk are only partly understood. Age-related accumulation of advanced glycation end products (AGEs) can activate chondrocytes and induce the production of proinflammatory cytokines and matrix metalloproteinases (MMPs). In the present study, we examined the effect of epigallocatechin-3-gallate (EGCG) on AGE-modified-BSA (AGE-BSA)-induced activation and production of TNFα and MMP-13 in human OA chondrocytes.     

Human articular chondrocytes express 15-lipoxygenase-1 and -2: potential role in osteoarthritis

Introduction  

15-Lipoxygenases and their metabolites have been shown to exhibit anti-inflammatory and immunomodulatory properties, but little is known regarding their expression and function in chondrocytes. The objective of this study was to evaluate the expression of 15-lipoxygenase-1 and -2 in human articular chondrocytes, and to investigate the effects of their metabolites 13(S)-hydroxy octadecadienoic and 15(S)-hydroxyeicosatetraenoic acids on IL-1β-induced matrix metalloproteinase (MMP)-1 and MMP-13 expression.     

Interleukin-1, tumor necrosis factor-alpha,and transforming growth factor-beta 1 and integrative meniscal repair: influences on meniscal cell proliferation and migration

Introduction  

Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) are up-regulated in injured and osteoarthritic knee joints. IL-1 and TNF-α inhibit integrative meniscal repair; however, the mechanisms by which this inhibition occurs are not fully understood. Transforming growth factor-β1 (TGF-β1) increases meniscal cell proliferation and accumulation, and enhances integrative meniscal repair. An improved understanding of the mechanisms modulating meniscal cell proliferation and migration will help to improve approaches for enhancing intrinsic or tissue-engineered repair of the meniscus. The goal of this study was to examine the hypothesis that IL-1 and TNF-α suppress, while TGF-β1 enhances, cellular proliferation and migration in cell and tissue models of meniscal repair.     

High mobility group box protein 1 in complex with lipopolysaccharide or IL-1 promotes an increased inflammatory phenotype in synovial fibroblasts

Introduction  

In addition to its direct proinflammatory activity, extracellular high mobility group box protein 1 (HMGB1) can strongly enhance the cytokine response evoked by other proinflammatory molecules, such as lipopolysaccharide (LPS), CpG-DNA and IL-1β, through the formation of complexes. Extracellular HMGB1 is abundant in arthritic joint tissue where it is suggested to promote inflammation as intra-articular injections of HMGB1 induce synovitis in mice and HMGB1 neutralizing therapy suppresses development of experimental arthritis. The aim of this study was to determine whether HMGB1 in complex with LPS, interleukin (IL)-1α or IL-1β has enhancing effects on the production of proinflammatory mediators by rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF). Furthermore, we examined the toll-like receptor (TLR) 4 and IL-1RI requirement for the cytokine-enhancing effects of the investigated HMGB1-ligand complexes.     

Cornel Iridoid Glycoside Inhibits Inflammation and Apoptosis in Brains of Rats with Focal Cerebral Ischemia

The capacity of cornel iridoid glycoside (CIG) to suppress the manifestations of ischemic stroke was investigated. CIG was administered to rats by the intragastric route once daily for 7 days. Focal cerebral ischemia was induced by 2 h of middle cerebral artery occlusion followed by 24 h of reperfusion. In non-treated rats large infarct areas were observed within 24 h of reperfusion. Examination of the ischemic cerebral cortex revealed microglia and astrocyte activation, increased interleukin-1β (IL-1 β) and tumor necrosis factor-α (TNF-α) concentrations, increased DNA fragmentation in the ischemia penumbra, elevated Bax expression, increased caspase-3 cleavage, and decreased Bcl-2 expression. Pretreatment with CIG decreased the infarct area, DNA fragmentation, IL-1β and TNF-α concentrations, microglia and astrocyte activation, Bax expression, and caspase-3 cleavage while increasing Bcl-2 expression. CIG exerts anti-neuroinflammatory and anti-apoptotic effects which should prove beneficial for prevention or treatment of stroke.     

Transforming growth factor β 869C/T and interleukin 6 -174G/C polymorphisms relate to the severity and progression of bone-erosive damage detected by ultrasound in rheumatoid arthritis

Introduction  

Single nucleotide polymorphisms (SNPs) of transforming growth factor β (TGF-β) and IL-6 genes (respectively, 869C/T and -174G/C) have been associated with radiographic severity of bone-erosive damage in patients with rheumatoid arthritis (RA). Musculoskeletal ultrasound (US) is more sensitive than radiography in detecting bone erosion. We analyzed the association between TGF-β 869C/T and IL-6 -174G/C SNPs and bone-erosive damage, evaluated by US, in a cohort of patients with severely active RA.     

Green tea polyphenol treatment is chondroprotective,anti-inflammatory and palliative in a mouse posttraumatic osteoarthritis model

Introduction

Epigallocatechin 3-gallate (EGCG), a polyphenol present in green tea, was shown to exert chondroprotective effects in vitro. In this study, we used a posttraumatic osteoarthritis (OA) mouse model to test whether EGCG could slow the progression of OA and relieve OA-associated pain.

Methods

C57BL/6 mice were subjected to surgical destabilization of the medial meniscus (DMM) or sham surgery. EGCG (25 mg/kg) or vehicle control was administered daily for 4 or 8 weeks by intraperitoneal injection starting on the day of surgery. OA severity was evaluated using Safranin O staining and Osteoarthritis Research Society International (OARSI) scores, as well as by immunohistochemical analysis to detect cleaved aggrecan and type II collagen and expression of proteolytic enzymes matrix metalloproteinase 13 (MMP-13) and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5). Real-time PCR was performed to characterize the expression of genes critical for articular cartilage homeostasis. During the course of the experiments, tactile sensitivity testing (von Frey test) and open-field assays were used to evaluate pain behaviors associated with OA, and expression of pain expression markers and inflammatory cytokines in the dorsal root ganglion (DRG) was determined by real-time PCR.

Results

Four and eight weeks after DMM surgery, the cartilage in EGCG-treated mice exhibited less Safranin O loss and cartilage erosion, as well as lower OARSI scores compared to vehicle-treated controls, which was associated with reduced staining for aggrecan and type II collagen cleavage epitopes, and reduced staining for MMP-13 and ADAMTS5 in the articular cartilage. Articular cartilage in the EGCG-treated mice also exhibited reduced levels of Mmp1, Mmp3, Mmp8, Mmp13,Adamts5, interleukin 1 beta (Il1b) and tumor necrosis factor alpha (Tnfa) mRNA and elevated gene expression of the MMP regulator Cbp/p300 interacting transactivator 2 (Cited2). Compared to vehicle controls, mice treated with EGCG exhibited reduced OA-associated pain, as indicated by higher locomotor behavior (that is, distance traveled). Moreover, expression of the chemokine receptor Ccr2 and proinflammatory cytokines Il1b and Tnfa in the DRG were significantly reduced to levels similar to those of sham-operated animals.

Conclusions

This study provides the first evidence in an OA animal model that EGCG significantly slows OA disease progression and exerts a palliative effect.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0508-y) contains supplementary material, which is available to authorized users.