Factors secreted by monosodium urate crystal-stimulated macrophages promote a proinflammatory state in osteoblasts: a potential indirect mechanism of bone erosion in gout.

Background: Tophi are lesions commonly present at sites of bone erosion in gout-affected joints. The tophus comprises a core of monosodium urate (MSU) crystals surrounded by soft tissue that contains macrophages and other immune cells. Previous studies found that MSU crystals directly reduce osteoblast viability and function.

Basic calcium phosphate crystals induce the expression of extracellular matrix remodelling enzymes in tenocytes.

Objectives: Basic calcium phosphate (BCP) crystals contribute to several syndromes associated with tendon disease, including acute calcific tendinitis and Milwaukee shoulder syndrome. Interactions between BCP crystals and tenocytes (tendon cells) may contribute to these clinical syndromes. This study aimed to determine the direct effects of BCP crystals on tenocyte function and viability.

Limitations of dual-energy CT in the detection of monosodium urate deposition in dense liquid tophi and calcified tophi.

Objective: Dual-energy CT (DECT) detection of monosodium urate (MSU) crystal deposition has demonstrated good sensitivity and specificity in patients with established gout. However, limitations have been reported with early disease and with low urate burden. We aimed to study the performance of DECT in the detection and quantification of MSU deposition in solid and liquid tophi.

Human Cartilage Homogenates Influence the Crystallization of Monosodium Urate and Inflammatory Response to Monosodium Urate Crystals: A Potential Link Between Osteoarthritis and Gout.

Objective: Monosodium urate (MSU) crystal deposition and gout flares frequently affect osteoarthritic joints. This study was undertaken to examine the effects of human cartilage homogenates on MSU crystallization and MSU crystal-induced inflammation.

Methods: Human cartilage homogenates were prepared from macroscopically healthy and macroscopically diseased knee joint samples.

Liposome-Mediated Drug Delivery in Larval Zebrafish to Manipulate Macrophage Function.

Chemical interventions are regularly used to examine and manipulate macrophage function in larval zebrafish. Given chemicals are typically administered by simple immersion or injection, it is not possible to resolve whether their impact on macrophage function is direct or indirect. Liposomes provide an attractive strategy to target drugs to specific cellular compartments, including macrophages.

Basic Calcium Phosphate Crystals Induce Osteoarthritis-Associated Changes in Phenotype Markers in Primary Human Chondrocytes by a Calcium/Calmodulin Kinase 2-Dependent Mechanism.

Chondrocytes in osteoarthritis undergo a phenotype shift leading to increased production of cartilage-degrading enzymes. There are similarities between the phenotype of osteoarthritic chondrocytes and those of growth plate chondrocytes. Hydroxyapatite can promote chondrocyte differentiation in the growth plate.

Greater insulin response to acute fructose ingestion among Māori and Pacific people compared to European people living in Aotearoa New Zealand.

Background: Fructose consumption has been linked with insulin resistance, obesity and diabetes, which are more prevalent in those of Māori or Pacific ethnicity compared to New Zealand European.

Aim: To determine whether the acute effects of fructose consumption on serum glucose, insulin, lipids and C-reactive protein differs according to body mass index (BMI) and/or ethnicity.

Methods: Participants of Māori (n = 25), Pacific (n = 26) or New Zealand European (n = 25) ethnicity consumed a 64 g fructose/16 g glucose solution.

Monosodium urate crystals reduce osteocyte viability and indirectly promote a shift in osteocyte function towards a proinflammatory and proresorptive state.

Background: Bone erosion is a frequent complication of gout and is strongly associated with tophi, which are lesions comprising inflammatory cells surrounding collections of monosodium urate (MSU) crystals. Osteocytes are important cellular mediators of bone remodeling. The aim of this study was to investigate the direct effects of MSU crystals and indirect effects of MSU crystal-induced inflammation on osteocytes.

Blocking fatty acid-fueled mROS production within macrophages alleviates acute gouty inflammation.

Gout is the most common inflammatory arthritis affecting men. Acute gouty inflammation is triggered by monosodium urate (MSU) crystal deposition in and around joints that activates macrophages into a proinflammatory state, resulting in neutrophil recruitment. A complete understanding of how MSU crystals activate macrophages in vivo has been difficult because of limitations of live imaging this process in traditional animal models.

Lactoferrin and parathyroid hormone are not harmful to primary tenocytes , but PDGF may be.

Introduction: Recently, bone-active factors such as parathyroid hormone and lactoferrin, have been used in pre-clinical models to promote tendon healing. How-ever, there is limited understanding of how these boneactive factors may affect the cells of the ten-don themselves. Here, we present an in vitro study assessing the effects of parathyroid hor-mone and lactoferrin on primary tendon cells (tenocytes), and compare their responses to the tenogenic factors, PDGF, IGF-1 and TGF-β.

Lack of Evidence that Soluble Urate Directly Influences Bone Remodelling: A Laboratory and Clinical Study.

Introduction: Numerous observational studies have reported that serum urate concentration positively correlates with bone density and reduced risk of fractures. The aim of this study was to examine whether soluble urate directly influences bone remodelling.

Methods: In laboratory studies, the in vitro effects of soluble urate were examined in osteoclast, osteoblast and osteocyte assays at a range of urate concentrations consistent with those typically observed in humans (up to 0.

Role of miR-146a in regulation of the acute inflammatory response to monosodium urate crystals.

Objectives: MicroRNAs (miRNA) are small non-coding RNAs that function as post-transcriptional repressors of gene expression. We hypothesised that miRNA regulate gene expression of proinflammatory cytokines in response to monosodium urate (MSU) crystals.

Methods: We stimulated human monocytic THP-1 cells with MSU crystals and examined miRNA and proinflammatory cytokine gene expression.

The effect of diet-induced obesity on the inflammatory phenotype of non-adipose-resident macrophages in an in vivo model of gout.

Objective: Gout is strongly associated with obesity. The aim of this study was to determine if obesity altered the inflammatory phenotype of non-adipose tissue-resident macrophages in response to the gout-causing agent monosodium urate (MSU) crystals.

Methods: C57BL/6J mice were fed a high-fat diet for 12 weeks.

Interactions between tenocytes and monosodium urate monohydrate crystals: implications for tendon involvement in gout.

Objectives: Advanced imaging studies have demonstrated that urate deposition in periarticular structures, such as tendons, is common in gout. The aim of this study was to investigate the effects of monosodium urate monohydrate (MSU) crystals on tenocyte viability and function.

Methods: The histological appearance of tendons in joints affected by advanced gout was examined using light microscopy.

Influence of the ABCG2 gout risk 141 K allele on urate metabolism during a fructose challenge.

Introduction: Both genetic variation in ATP-binding cassette sub-family G member 2 (ABCG2) and intake of fructose-containing beverages are major risk factors for hyperuricemia and gout. This study aimed to test the hypothesis that the ABCG2 gout risk allele 141 K promotes the hyperuricaemic response to fructose loading.

Methods: Healthy volunteers (n = 74) provided serum and urine samples immediately before and 30, 60, 120 and 180 minutes after ingesting a 64 g fructose solution.

Myeloid-related proteins 8 and 14 contribute to monosodium urate monohydrate crystal-induced inflammation in gout.

Objective: Monosodium urate monohydrate (MSU) crystal-induced interleukin-1β (IL-1β) secretion is a critical factor in the pathogenesis of gout. However, without costimulation by a proIL-1β-inducing factor, MSU crystals alone are insufficient to induce IL-1β secretion. The responsible costimulatory factors that act as a priming endogenous signal in vivo are not yet known.

The effects of monosodium urate monohydrate crystals on chondrocyte viability and function: implications for development of cartilage damage in gout.

Objective: Cartilage damage is frequently observed in advanced destructive gout. The aim of our study was to investigate the effects of monosodium urate monohydrate (MSU) crystals on chondrocyte viability and function.

Methods: The alamarBlue assay and flow cytometry were used to assess the viability of primary human chondrocytes and cartilage explants following culture with MSU crystals.

Population-specific influence of SLC2A9 genotype on the acute hyperuricaemic response to a fructose load.

Background: SLC2A9 is a strong genetic risk factor for hyperuricaemia and gout. SLC2A9 (GLUT9) is a high capacity urate transporter and reportedly transports glucose and fructose. Intake of fructose-containing beverages is associated with development of hyperuricaemia and gout.

No reduction in circulating preosteoclasts 18 months after treatment with zoledronate: analysis from a randomized placebo controlled trial.

The conventional model that bisphosphonates bind to the bone surface and inhibit mature osteoclasts does not convincingly explain the prolonged duration of action of zoledronate. We hypothesized that zoledronate on the bone surface adjacent to marrow cells impairs osteoclastogenesis, contributing to sustained inhibition of resorption. In this case, numbers of circulating preosteoclasts may be reduced after zoledronate treatment.

Monosodium urate monohydrate crystals inhibit osteoblast viability and function: implications for development of bone erosion in gout.

Background: Bone erosion is a common manifestation of chronic tophaceous gout.

Objectives: To investigate the effects of monosodium urate monohydrate (MSU) crystals on osteoblast viability and function.

Methods: The MTT assay and flow cytometry were used to assess osteoblast cell viability in the MC3T3-E1 and ST2 osteoblast-like cell lines, and primary rat and primary human osteoblasts cultured with MSU crystals.

Circulating mediators of bone remodeling in psoriatic arthritis: implications for disordered osteoclastogenesis and bone erosion.

Introduction: Diverse bone pathologies are observed in patients with psoriatic arthritis (PsA). Uncoupling of bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of PsA. The aim of this study was to examine the role of soluble mediators of bone remodeling within the circulation of patients with PsA.

Acute effect of milk on serum urate concentrations: a randomised controlled crossover trial.

Objectives: Recent observational studies have highlighted the beneficial role of dairy ingestion in gout prevention. The aims of this study were to determine the acute effects of milk ingestion on serum urate concentrations and examine the mechanisms of these effects.

Methods: This was a short-term randomised controlled crossover trial of milk in 16 healthy male volunteers.

Cellular characterization of the gouty tophus: a quantitative analysis.

Objective: To characterize the cellular architecture of the tophus and to determine the presence of cytokines implicated in the initiation and resolution of gouty inflammation.

Methods: Sixteen fixed, paraffin-embedded, uninfected tophus samples were surgically obtained from 12 patients with microscopically proven gout and were analyzed by quantitative immunohistochemistry. The number of cells present in the corona and fibrovascular zones of the tophus was analyzed by Genmod mixed models analysis.

Identification of dairy fractions with anti-inflammatory properties in models of acute gout.

Aims: Large epidemiological studies have shown that low-fat dairy intake reduces the risk of developing gout. It was hypothesised that factors within dairy fractions inhibit the inflammatory response to monosodium urate monohydrate (MSU) crystals.

Methods: Dairy fractions were tested in MSU crystal-stimulated THP-1 cell assays.