Pro-fibrotic phenotype of bone marrow stromal cells in Modic type 1 changes.

Modic type 1 changes (MC1) are painful vertebral bone marrow lesions frequently found in patients suffering from chronic low-back pain. Marrow fibrosis is a hallmark of MC1. Bone marrow stromal cells (BMSCs) are key players in other fibrotic bone marrow pathologies, yet their role in MC1 is unknown.

Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen .

Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1β, may be further evidence of the role of the anaerobic bacterium (previously ) in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1β, and other known IL-1β-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with for up to 48 h. Upon infection, significant upregulation of IL-1β, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls.

Location, location, location: how the tissue microenvironment affects inflammation in RA.

Current treatments for rheumatoid arthritis (RA) do not work well for a large proportion of patients, or at all in some individuals, and cannot cure or prevent this disease. One major obstacle to developing better drugs is a lack of complete understanding of how inflammatory joint disease arises and progresses. Emerging evidence indicates an important role for the tissue microenvironment in the pathogenesis of RA.

Epigenetics, pregnancy and autoimmune rheumatic diseases.

Autoimmune rheumatic diseases (ARDs) are chronic conditions with a striking female predominance, frequently affecting women of childbearing age. Sex hormones and gender dimorphism of immune response are major determinants in the multifactorial pathogenesis of ARDs, with significant implications throughout reproductive life. Particularly, pregnancy represents a challenging condition in the context of autoimmunity, baring profound hormonal and immunologic changes, which are responsible for the bi-directional interaction between ARDs outcome and pregnancy course.

Characterization of Plasma-Derived Small Extracellular Vesicles Indicates Ongoing Endothelial and Platelet Activation in Patients with Thrombotic Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease, characterized by thrombosis, obstetric complications and the presence of antiphospholipid antibodies (aPL), which drive endothelial injury and thrombophilia. Extracellular vesicles (EVs) have been implicated in endothelial and thrombotic pathologies. Here, we characterized the quantity, cellular origin and the surface expression of biologically active molecules in small EVs (sEVs) isolated from the plasma of thrombotic APS patients ( = 14), aPL-negative patients with idiopathic thrombosis (aPL-neg IT, = 5) and healthy blood donors (HBD, = 7).

Evaluation of botulinum toxin A injections for the treatment of refractory chronic digital ulcers in patients with systemic sclerosis.

Objectives: To evaluate the therapeutic benefit of botulinum toxin A (BTX-A) injections for digital ulcers (DU) in patients with systemic sclerosis (SSc).

Methods: A systematic literature review was performed and the identified articles were selected by two reviewers and analysed with respect to date of publication, inclusion and exclusion criteria, number and age of participants, volume of BTX-A, injection sites, outcomes, and adverse events. In addition, in the Zurich cohort, 7 SSc patients were eligible for the study and were assessed for the duration of DU to heal, duration of DU-free periods, changes in frequency and numbers of prescribed vasodilators, pain and blood flow.

Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis.

Objectives: Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database.

Methods: Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12±3 months.

Why location matters - site-specific factors in rheumatic diseases.

Rheumatic diseases follow a characteristic anatomical pattern of joint and organ involvement. This Review explores three interconnected mechanisms that might be involved in the predilection of specific joints for developing specific forms of arthritis: site-specific local cell types that drive disease; systemic triggers that affect local cell types; and site-specific exogenous factors, such as focal mechanical stress, that activate cells locally. The embryonic development of limbs and joints is also relevant to the propensity of certain joints to develop arthritis.

MicroRNAs interfere with DNA methylation in rheumatoid arthritis synovial fibroblasts.

Background: The DNA of rheumatoid arthritis synovial fibroblasts (RASF) is globally hypomethylated; this contributes to an aggressive behaviour. In an attempt to remethylate these cells, we supplemented with methyl donors. We investigated the possible interference of microRNAs (miRs).

Epigenetic biomarkers in rheumatology - the future?

Epigenetic changes are stable modifications of DNA or histones that profoundly alter gene expression. They can be changed by environmental influences and can then be passed on to daughter cells or via the germ line to offspring. A variety of changes in epigenetic marks and in the expression of noncoding RNA has been found in cancer as well as in chronic inflammatory diseases.

Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis.

Background: Identification of parameters for early diagnosis and treatment response would be beneficial for patients with early rheumatoid arthritis (ERA) to prevent ongoing joint damage. miRNAs have features of potential biomarkers, and an altered expression of miRNAs was shown in established rheumatoid arthritis (RA).

Objective: To analyse RA associated miRNAs in the sera of patients with ERA to find markers of early disease, clinical activity or predictors of disease outcome.

Effect of the oral application of a highly selective MMP-13 inhibitor in three different animal models of rheumatoid arthritis.

Objective: To evaluate the decrease of cartilage destruction by a novel orally active and specific matrix metalloproteinase 13 (MMP-13) inhibitor in three different animal models of rheumatoid arthritis (RA).

Materials And Methods: The SCID mouse co-implantation model of RA, the collagen-induced arthritis (CIA) model in mice and the antigen-induced arthritis model (AIA) in rabbits were used.

Results: In the SCID mouse co-implantation model, the MMP-13 inhibitor reduced cartilage destruction by 75%.

Trichostatin A sensitises rheumatoid arthritis synovial fibroblasts for TRAIL-induced apoptosis.

Background: Histone acetylation/deacetylation has a critical role in the regulation of transcription by altering the chromatin structure.

Objective: To analyse the effect of trichostatin A (TSA), a streptomyces metabolite which specifically inhibits mammalian histone deacetylases, on TRAIL-induced apoptosis of rheumatoid arthritis synovial fibroblasts (RASF).

Methods: Apoptotic cells were detected after co-treatment of RASF with TRAIL (200 ng/ml) and TSA (0.

p53 in rheumatoid arthritis synovial fibroblasts at sites of invasion.

Objective: To analyse the functional response of p53 in rheumatoid arthritis synovial fibroblasts (RASF) in vitro and in vivo and to investigate whether activation of p53 modulates the destructive process of RASF.

Methods: RASF and controls grown on chamber slides were either directly examined with DO7 anti-p53 antibodies by immunofluorescence or irradiated with 10 Gy x rays and analysed time dependently for the expression of p53. The percentage of positive cells was evaluated by a quantitative scoring system.

Prevalence of TTV DNA and GBV-C RNA in patients with systemic sclerosis, rheumatoid arthritis, and osteoarthritis does not differ from that in healthy blood donors.

Objective: To determine the prevalence of GB virus-C (GBV-C) RNA and TT virus (TTV) DNA in patients with systemic sclerosis (SSc), rheumatoid arthritis (RA), and osteoarthritis (OA) as well as to compare the autoantibody pattern in patients with SSc with and without evidence of viral infection.

Patients And Methods: The study included 168 patients (84 SSc, 41 RA, and 43 OA) diagnosed according to the American College of Rheumatology criteria and 122 volunteer blood donors. The presence of GBV-C RNA and TTV DNA in serum was assessed by nested reverse transcriptase-polymerase chain reaction (RT-PCR) and semi-nested PCR, respectively.