Inhibition of Human Osteoclast Differentiation by Kynurenine through the Aryl-Hydrocarbon Receptor Pathway.

Aryl-hydrocarbon receptor (AhR) is a ligand-activated transcription factor and regulates differentiation and function of various immune cells such as dendritic cells, Th17, and regulatory T cells. In recent studies, it was reported that AhR is involved in bone remodeling through regulating both osteoblasts and osteoclasts. However, the roles and mechanisms of AhR activation in human osteoclasts remain unknown.

Augmenting MNK1/2 activation by c-FMS proteolysis promotes osteoclastogenesis and arthritic bone erosion.

Osteoclasts are bone-resorbing cells that play an essential role in homeostatic bone remodeling and pathological bone erosion. Macrophage colony stimulating factor (M-CSF) is abundant in rheumatoid arthritis (RA). However, the role of M-CSF in arthritic bone erosion is not completely understood.

The Role of Aryl-Hydrocarbon Receptor (AhR) in Osteoclast Differentiation and Function.

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays a crucial role in bone remodeling through altering the interplay between bone-forming osteoblasts and bone-resorbing osteoclasts. While effects of AhR signaling in osteoblasts are well understood, the role and mechanism of AhR signaling in regulating osteoclastogenesis is not widely understood. AhR, when binding with exogenous ligands (environmental pollutants such as polycylic aryl hydrocarbon (PAH), dioxins) or endogenous ligand indoxyl-sulfate (IS), has dual functions that are mediated by the nature of the binding ligand, binding time, and specific pathways of distinct ligands.

1,25-Dihydroxyvitamin D induces human myeloid cell differentiation via the mTOR signaling pathway.

1,25-Dihydroxyvitamin D or 1,25(OH)D is known to play an important role in the differentiation of human myeloid cells. However, the molecular mechanism underlying the 1,25(OH)D-mediated differentiation of human myeloid cells is incompletely understood. Here, we report that 1,25(OH)D induces differentiation of human myeloid cell lines such as U937 and THP-1 cells via the mammalian target of rapamycin (mTOR) signaling pathway.

A dual role of TGF-β in human osteoclast differentiation mediated by Smad1 versus Smad3 signaling.

TGF-β1 is highly expressed in the synovial tissue of patients with rheumatoid arthritis and is known as a cytokine that plays an important role in tissue repair and immune cell regulation. However, the role of TGF-β1 is still unclear in osteoclastogenesis. In this study, we examined the effect of TGF-β1 on osteoclast differentiation and the underlying mechanism using healthy human peripheral blood monocytes.

Poly-γ-glutamic acid suppresses osteoclastogenesis in human osteoclast precursors and prevents joint damage in a collagen-induced murine arthritis model.

Poly-γ-glutamic acid (γ-PGA), a natural polymer derived from Bacillus subtilis, shows anti-inflammatory activity. However, the effects of γ-PGA on osteoclasts, which are important cells for joint destruction in inflammatory diseases such as rheumatoid arthritis (RA), have not yet been reported. In this study, we show that γ-PGA markedly inhibits osteoclast differentiation in normal PBMC-derived osteoclast precursors and in synovial fluid macrophages of patients with RA.

Metabolic syndrome: prevalence and risk factors in Korean gout patients.

Background/aims: We performed this study to investigate associations between metabolic syndrome, chronic kidney disease (CKD), and gout.

Methods: We reviewed the medical records of 151 patients with gout at the Department of Rheumatology in Korea University Ansan Hospital. The following measures were examined: waist circumference, blood pressure, alcohol consumption, and levels of triglyceride, high density lipoprotein cholesterol, fasting serum glucose, serum uric acid (SUA), creatinine, insulin, and C-peptide.

Associations between functional FCGR2A R131H and FCGR3A F158V polymorphisms and responsiveness to TNF blockers in spondyloarthropathy, psoriasis and Crohn's disease: a meta-analysis.

Aim: The aim of the current study was to investigate whether FCGR polymorphisms are associated with responsiveness to anti-TNF-α therapy in patients with spondyloarthropathy, psoriasis, and Crohn's disease.

Materials & Methods: We conducted a meta-analysis to evaluate the association between the functional FCGR3A F158V and FCGR2A R131H polymorphisms and responsiveness to TNF blockers.

Results: The meta-analysis indicated that responsiveness to TNF blockers was associated with the FCGR3A V allele (odds ratio: 3.

Association between the three functional miR-146a single-nucleotide polymorphisms, rs2910164, rs57095329, and rs2431697, and autoimmune disease susceptibility: A meta-analysis.

Studies suggest associations between the miR-146a single nucleotide polymorphisms (SNPs) and susceptibility to autoimmune diseases. However, the results are inconsistent and inconclusive. Therefore, the aim of this study was to arrive at a conclusion about the association between the three functional miR-146a SNPs and autoimmune disease risk.

Unique gene expression profile in osteoarthritis synovium compared with cartilage: analysis of publicly accessible microarray datasets.

The purpose of this study was to identify a gene expression signature in osteoarthritis (OA) synovium and genomic pathways likely to be involved in the pathogenesis of OA. Four publicly accessible microarray studies from synovium of OA patients were integrated, and a transcriptomic and network-based meta-analysis was performed. Based on pathways according to the Kyoto Encyclopedia of Genes and Genomes, functional enrichment analysis was performed.

Panenteritis as an Initial Presentation of Systemic Lupus Erythematosus.

Lupus enteritis is a rare, severe complication of systemic lupus erythematosus (SLE), needing prompt diagnosis and proper management. However, SLE rarely presents as lupus enteritis at the time of initial diagnosis. Thus, delayed diagnosis and misdiagnosis are common.

Calcium channels: the potential therapeutic targets for inflammatory bone destruction of rheumatoid arthritis.

Introduction: Inflammatory bone resorption causes progressive joint destruction which ultimately leads to functional disability in rheumatoid arthritis (RA). The primary cell responsible for bone resorption is the osteoclast, which means it is a potential therapeutic target against bone destruction. In fact, experimental and clinical findings suggest that blockade of osteoclast differentiation and function is highly effective in inhibiting bone destruction in RA.

Relative efficacy and tolerability of etoricoxib, celecoxib, and naproxen in the treatment of osteoarthritis : A Bayesian network meta-analysis of randomized controlled trials based on patient withdrawal.

Aims: This study aimed to assess the relative efficacy and tolerability of etoricoxib, celecoxib, and naproxen at recommended dosages in patients with osteoarthritis (OA).

Methods: Randomized controlled trials (RCTs) examining the efficacy and tolerability of etoricoxib 30-60 mg, celecoxib 200-400 mg, and naproxen 1000 mg, based on the number of patient withdrawals among those with OA, were included in this network meta-analysis. We performed a Bayesian random-effects network meta-analysis to combine direct and indirect evidence from the RCTs.

Association between FCGR3B copy number variations and susceptibility to autoimmune diseases: a meta-analysis.

Objective: This study determined whether FCGR3B copy number variations (CNVs) were associated with susceptibility to autoimmune diseases.

Methods: A meta-analysis was conducted to determine the association between FCGR3B CNVs and susceptibility to autoimmune diseases by comparing low FCGR3B CN (<2 to ≥2) and high FCGR3B CN (>2 to ≤2).

Results: In all, 28 comparative studies from 15 reports involving 12,160 patients and 11,103 controls were included in this meta-analysis.

Association between IL-6 -174 G/C, IL-6 -634 G/C, and IFN-γ +874 A/T polymorphisms and susceptibility to recurrent pregnancy loss: a meta-analysis.

Objective: The aim of this study was to determine whether interleukin-6 (IL-6) -174 G/C, IL-6 -634 G/C, and interferon-γ (IFN-γ) +874 A/T polymorphisms are associated with susceptibility to recurrent pregnancy loss (RPL).

Methods: We conducted a literature search using PubMed and EMBASE databases and performed a meta-analysis using fixed- or random-effects models.

Results: A total of 15 articles met the study inclusion criteria.

Association between TNF-α (-308 A/G, -238 A/G, -857 C/T) polymorphisms and responsiveness to TNF-α blockers in spondyloarthropathy, psoriasis and Crohn's disease: a meta-analysis.

Aim: The aim of this study is to investigate whether TNF-α polymorphisms are associated with the responsiveness to anti-TNF-α therapy in patients with spondyloarthropathy, psoriasis, and Crohn's disease.

Methods: We conducted a meta-analysis on the association between the TNF-α polymorphisms and responsiveness of patients.

Results: The meta-analysis indicated an association between the TNF-α -308 G allele (OR = 2.

Meta-analysis of associations between MTHFR and GST polymorphisms and susceptibility to multiple sclerosis.

We examined whether methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) polymorphisms are associated with susceptibility to multiple sclerosis (MS). We performed a meta-analysis on the association between MS and the following genotypes: MTHFR C677T, A1298C, and GSTP1 A313G polymorphisms, and GSTM1 and GSTT1 null alleles. Fifteen comparisons involving 2,486 patients and 2,861 controls were considered.

Association between TNF-α promoter -308 A/G polymorphism and Alzheimer's disease: a meta-analysis.

The aim of this study was to determine whether the tumor necrosis factor-α (TNF-α) promoter -308 A/G polymorphism is associated with susceptibility to Alzheimer's disease (AD) in multi-ethnic populations. MEDLINE and EMBASE databases and manual literature search were used to identify published articles in which TNF-α polymorphism was determined in AD patients and control subjects. Meta-analysis was conducted on the association between the TNF-α -308 A/G polymorphism and AD using allele contrast and the recessive, dominant, and additive models.

1α,25-Dihydroxyvitamin D3 upregulates HIF-1 and TREM-1 via mTOR signaling.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is induced by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) in human monocytes/macrophages and epithelial cells. However, little information is available regarding the mechanism of 1,25(OH)2D3-induced TREM-1 expression in human monocytes/macrophages. In this study, 1,25(OH)2D3 was shown to strongly upregulate hypoxia-inducible transcription factor (HIF) in PMA-differentiated U937 cells.

Paraoxonase 1 Q192R and L55M polymorphisms and susceptibility to amyotrophic lateral sclerosis: a meta-analysis.

This study aimed to investigate whether paraoxonase 1 (PON1) Q192R and L55M polymorphisms are associated with susceptibility to amyotrophic lateral sclerosis (ALS). We conducted a meta-analysis of the associations between the PON1 Q192R and L55M polymorphisms and ALS. A total of 2,831 patients and 3,123 controls from eight studies of the PON1 Q192R polymorphism and seven studies of the PON1 L55M T polymorphism were considered for this study.