Coping strategies and depressiveness in primary systemic vasculitis--what is their impact on health-related quality of life?

Objective: To investigate the influence of disease-related coping strategies and depressiveness on health-related quality of life (HRQOL) in primary systemic vasculitis (PSV) patients.

Methods: One hundred and twenty-two patients with definite diagnosis of PSV were examined in a cross-sectional study. HRQOL (SF-36), depressiveness (BDI), illness perception (B-IPQ) and coping strategies (FKV-LIS) were measured using validated instruments.

Heat shock protein 90 (Hsp90) inhibition targets canonical TGF-β signalling to prevent fibrosis.

Objectives: Targeted therapies for systemic sclerosis (SSc) and other fibrotic diseases are not yet available. We evaluated the efficacy of heat shock protein 90 (Hsp90) inhibition as a novel approach to inhibition of aberrant transforming growth factor (TGF)-β signalling and for the treatment of fibrosis in preclinical models of SSc.

Methods: Expression of Hsp90 was quantified by quantitative PCR, western blot and immunohistochemistry.

PPARβ/δ governs Wnt signaling and bone turnover.

Peroxisome proliferator-activated receptors (PPARs) act as metabolic sensors and central regulators of fat and glucose homeostasis. Furthermore, PPARγ has been implicated as major catabolic regulator of bone mass in mice and humans. However, a potential involvement of other PPAR subtypes in the regulation of bone homeostasis has remained elusive.

Idiopathic hand osteoarthritis vs haemochromatosis arthropathy--a clinical, functional and radiographic study.

Objective: Haemochromatosis arthropathy is a secondary OA and the most frequent and earliest clinical presentation of hereditary haemochromatosis (HH). The aim of this study was to perform a direct clinical, functional and radiographic comparison with idiopathic hand OA (HOA) to unravel important differences between these clinical entities.

Methods: In total, 299 patients (141 with HH arthropathy of the hands and 158 patients with idiopathic HOA) were recruited.

Morphogen pathways in systemic sclerosis.

The morphogen pathways Wnt, hedgehog, and Notch are key regulators of organ development and tissue homeostasis. In adults, the tightly regulated activity of morphogen pathways is essential for cell renewal and tissue regeneration. Loss of control and persistent activation of morphogen pathways, however, can lead to a variety of diseases, including malignancy and fibrotic disorders.

The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium.

Background: Interleukin (IL)-36α is a recently described member of the IL-1 cytokine family with pro-inflammatory and clearly pathogenic properties in psoriasis.

Objective: To determine the IL-36α expression in psoriatic arthritis (PsA) compared to rheumatoid arthritis (RA) and osteoarthritis (OA).

Methods: Synovial tissues obtained from arthritis patients were stained for IL-36α, IL-36 receptor (IL-36R) and IL-36R antagonist (IL-36Ra) by immunohistochemistry and immunofluorescence.

Mitogen-activated protein kinase 2 regulates physiological and pathological bone turnover.

The objective of this study was to investigate the role of the serine-threonine kinase mitogen-activated protein kinase 2 (MK2) in bone homeostasis. Primary bone cell cultures from MK2(+/+) and MK2(-/-) mice were assessed for osteoclast and osteoblast differentiation, bone resorption, and gene expression. Bone architecture of MK2(+/+) and MK2(-/-) mice was investigated by micro-computed tomography and histomorphometry.

Inactivation of tankyrases reduces experimental fibrosis by inhibiting canonical Wnt signalling.

Objectives: Canonical Wnt signalling has recently emerged as a key mediator of fibroblast activation and tissue fibrosis in systemic sclerosis. Here, we investigated tankyrases as novel molecular targets for inhibition of canonical Wnt signalling in fibrotic diseases.

Methods: The antifibrotic effects of the tankyrase inhibitor XAV-939 or of siRNA-mediated knockdown of tankyrases were evaluated in the mouse models of bleomycin-induced dermal fibrosis and in experimental fibrosis induced by adenoviral overexpression of a constitutively active TGF-β receptor I (Ad-TBRI).

12/15-lipoxygenase during the regulation of inflammation, immunity, and self-tolerance.

12/15-Lipoxygenase (12/15-LO) catalyzes the oxidation of free and esterified fatty acids thereby generating a whole spectrum of bioactive lipid mediators. This enzyme is involved in the regulation of various homeostatic processes as well as in the pathogenesis of multiple diseases. During the innate and adaptive immune response, 12/15-LO and its products exert both pro- and anti-inflammatory effects.

Moonlighting osteoclasts as undertakers of apoptotic cells.

Rapid clearance of apoptotic cells, frequently referred to as efferocytosis, is crucial for the maintenance of tissue homeostasis and the prevention of autoimmunity. The common model of apoptotic cell clearance involves a system of released "Find me" and exposed "Eat me" signals on apoptotic cells, detected and recognized by matching receptors on macrophages or dendritic cells (DC), referred to as the phagocytic synapse. Osteoclasts share the monocyte lineage with these professional mononuclear phagocytes, thus raising the question if, in addition to bone resorption, osteoclasts can act as scavengers for apoptotic cells.

Measuring pain and efficacy of pain treatment in inflammatory arthritis: a systematic literature review.

Objective: To systematically review the available literature on measuring pain and the efficacy of pain treatment in inflammatory arthritis (IA), as an evidence base for generating clinical practice recommendations.

Methods: A systematic literature search was performed in Medline, Embase, Cochrane Library, and the American College of Rheumatology/European League Against Rheumatism 2008/2009 meeting abstracts, searching for studies evaluating clinimetric properties of pain measurement tools in IA (convergent validity, internal consistency, retest reliability, responsiveness, feasibility, and standardization). Studies that presented information on these properties were reviewed and their data were integrated into the pool of results available for pain measures in IA.

Inhibition of H3K27 histone trimethylation activates fibroblasts and induces fibrosis.

Objectives: Epigenetic modifications such as DNA methylation and histone acetylation have been implicated in the pathogenesis of systemic sclerosis. However, histone methylation has not been investigated so far. We therefore aimed to evaluate the role of the trimethylation of histone H3 on lysine 27 (H3K27me3) on fibroblast activation and fibrosis.

Pomalidomide is effective for prevention and treatment of experimental skin fibrosis.

Objectives: Tissue fibrosis is a major hallmark and a leading cause of death in systemic sclerosis (SSc). Here, we investigated the antifibrotic effects of pomalidomide, an analogue of thalidomide with potent immunomodulatory effects, in preclinical models of skin fibrosis.

Methods: We evaluated the antifibrotic effects of pomalidomide in preventive as well as therapeutic treatment regimes using bleomycin-induced dermal fibrosis as a model of early, inflammatory stages of fibrosis and the tight-skin mouse model as a model of later stages of fibrosis with endogenous activation of fibroblasts.

Tyrosine kinase signaling in fibrotic disorders: Translation of basic research to human disease.

Tyrosine kinases regulate a broad variety of physiological cell processes, including metabolism, growth, differentiation and apoptosis. Abnormal tyrosine kinase activity disturbs the physiological cell homeostasis and can lead to cancer, vascular disease, and fibrosis. In regard to fibrosis, different tyrosine kinases have been identified as determinants of disease progression and potential targets for anti-fibrotic therapies.

Pathways for bone loss in inflammatory disease.

Chronic inflammation including autoimmune disease is an important risk factor for the development of osteoporosis. Receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) play a central role in osteoclast differentiation and function, and the molecular pathways by which M-CSF and RANKL induce osteoclast differentiation have been analyzed in detail. Proinflammatory cytokines directly or indirectly regulate osteoclastogenesis and bone resorption providing a link between inflammation and osteoporosis.

12/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance.

Noninflammatory clearance of apoptotic cells (ACs) is crucial to maintain self-tolerance. Here, we have reported a role for the enzyme 12/15-lipoxygenase (12/15-LO) as a central factor governing the sorting of ACs into differentially activated monocyte subpopulations. During inflammation, uptake of ACs was confined to a population of 12/15-LO-expressing, alternatively activated resident macrophages (resMΦ), which blocked uptake of ACs into freshly recruited inflammatory Ly6C(hi) monocytes in a 12/15-LO-dependent manner.

Activation of canonical Wnt signalling is required for TGF-β-mediated fibrosis.

The transforming growth factor-β (TGF-β) signalling pathway is a key mediator of fibroblast activation that drives the aberrant synthesis of extracellular matrix in fibrotic diseases. Here we demonstrate a novel link between transforming growth factor-β and the canonical Wnt pathway. TGF-β stimulates canonical Wnt signalling in a p38-dependent manner by decreasing the expression of the Wnt antagonist Dickkopf-1.

Blockade of the hedgehog pathway inhibits osteophyte formation in arthritis.

Background: Osteophyte formation is a common phenomenon in arthritis. Bone formation by endochondral ossification is considered a key pathophysiological process in the formation of osteophytes.

Objective: To examine the hypothesis that inhibition of smoothened (Smo), a key component of the hedgehog pathway inhibits osteophyte formation as the hedgehog pathway mediates endochondral ossification.

Anti IL-17A therapy inhibits bone loss in TNF-α-mediated murine arthritis by modulation of the T-cell balance.

Tumour necrosis factor alpha (TNF-α) is a major inducer for inflammation and bone loss. Here, we investigated whether interleukin (IL)-17 plays a role in TNF-α-mediated inflammation and bone resorption. Human TNF-α transgenic (hTNFtg) mice were treated with a neutralizing anti-IL-17A antibody and assessed for inflammation, cartilage and bone damage.

Pathophysiology of spondyloarthritis.

Spondyloarthritis (SpA) is characterized by inflammation and new bone formation in the spine and entheses. The disease is the result of a complex interplay among susceptibility genes, microbial triggers, inflammation of bone marrow, and the enthesial structures and new bone formation. This article gives a conceptual overview of the major insights into the pathophysiology of SpA and discusses the main genes associated with SpA, as well as other factors that are involved in the onset of inflammation.

Structural bone changes in spondyloarthritis: mechanisms, clinical impact and therapeutic considerations.

Spondyloarthritis (SpA) is an inflammatory disease of the spine, the peripheral joints and the entheses and shares some clinical features with rheumatoid arthritis (RA). Chronic inflammation of musculoskeletal structures leads to disease symptoms such as pain and stiffness and structural changes in the bone tissue. Furthermore, therapies for SpA are based on those for RA, which attempt to inhibit synovial inflammation that leads to retardation or even arrest of structural damage.

Eotaxin-3 in Churg-Strauss syndrome: a clinical and immunogenetic study.

Objectives: To determine the potential of eotaxin-3 as a diagnostic marker for active disease and genetic susceptibility factor for Churg-Strauss syndrome (CSS).

Methods: A total of 37 patients with active, relapsed or inactive CSS, 123 healthy controls and 138 disease controls were studied. Clinical data were collected and serum levels of eotaxin-3 were determined.

A comparative study of periarticular bone lesions in rheumatoid arthritis and psoriatic arthritis.

Background: Psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are both destructive arthritides but may differ substantially in their periarticular bone changes.

Objectives: To investigate the differences in the structural changes of periarticular bone in patients with PsA and RA by a high-resolution imaging technique designed to visualise the bone architecture.

Methods: 30 patients with PsA and 58 patients with RA received a µCT scan to compare structural bone changes in the metacarpophalangeal joints of the dominantly affected hand.

Pharmacotherapy: concepts of pathogenesis and emerging treatments. Novel targets in bone and cartilage.

The spectrum of arthritis ranges from erosive (e.g., rheumatoid arthritis) to ossifying disease with formation of new bone (e.

Antibodies to the endoplasmic reticulum-resident chaperones calnexin, BiP and Grp94 in patients with rheumatoid arthritis and systemic lupus erythematosus.

Objectives: To investigate the presence of autoantibodies against mammalian chaperones of the endoplasmic reticulum (ER) in patients with RA and other immune-mediated diseases.

Methods: Sera from healthy donors, from early RA patients with two follow-up samples, patients with SLE, SSc and IBD were collected and analysed for anti-ER chaperone antibodies. Detection of serum IgG antibodies against immunoglobulin heavy chain binding protein (BiP), glucose-regulated protein 94 (Grp94) and calnexin was carried out using ELISA.