Chemokine signals are crucial for enhanced homing and differentiation of circulating osteoclast progenitor cells

Abstract Background The peripheral blood (PB) monocyte pool contains osteoclast progenitors (OCPs), which contribute to osteoresorption in inflammatory arthritides and are influenced by the cytokine and chemokine milieu. We aimed to define the importance of chemokine signals for migration and activation of OCPs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Methods PB and, when applicable, synovial fluid (SF) samples were collected from 129 patients with RA, 53 patients with PsA, and 110 control patients in parallel to clinical parameters of disease activity, autoantibody levels, and applied therapy. Receptors for osteoclastogenic factors (CD115 and receptor activator of nuclear factor-κB [RANK]) and selected chemokines (CC chemokine receptor 1 [CCR1], CCR2, CCR4, CXC chemokine receptor 3 [CXCR3], CXCR4) were determined in an OCP-rich subpopulation (CD3−CD19−CD56−CD11b+CD14+) by flow cytometry. In parallel, levels of CC chemokine ligand 2 (CCL2), CCL3, CCL4, CCL5, CXC chemokine ligand 9 (CXCL9), CXCL10, and CXCL12 were measured using cytometric bead array or enzyme-linked immunosorbent assay. Sorted OCPs were stimulated in culture by macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand, and they were differentiated into mature osteoclasts that resorb bone. Selected chemokines (CCL2, CCL5, CXCL10, and CXCL12) were tested for their osteoclastogenic and chemotactic effects on circulatory OCPs in vitro. Results The OCP population was moderately enlarged among PB cells in RA and correlated with levels of tumor necrosis factor-α (TNF-α), rheumatoid factor, CCL2, and CCL5. Compared with PB, the RANK+ subpopulation was expanded in SF and correlated with the number of tender joints. Patients with PsA could be distinguished by increased RANK expression rather than total OCP population. OCPs from patients with arthritis had higher expression of CCR1, CCR2, CCR4, CXCR3, and CXCR4. In parallel, patients with RA had increased levels of CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10, with significant elevation in SF vs PB for CXCL10. The subset expressing CXCR4 positively correlated with TNF-α, bone resorption marker, and rheumatoid factor, and it was reduced in patients treated with disease-modifying antirheumatic drugs. The CCR4+ subset showed a significant negative trend during anti-TNF treatment. CCL2, CCL5, and CXCL10 had similar osteoclastogenic effects, with CCL5 showing the greatest chemotactic action on OCPs. Conclusions In our study, we identified distinct effects of selected chemokines on stimulation of OCP mobilization, tissue homing, and maturation. Novel insights into migratory behaviors and functional properties of circulatory OCPs in response to chemotactic signals could open ways to new therapeutic targets in RA

Health-related quality of life among patients with postmenopausal osteoporosis treated with weekly and monthly bisphosphonates

OBJECTIVE: The present study was designed to assess the effect of monthly ibandronate on health-related quality of life (HR-QoL) in patients with postmenopausal osteoporosis previously treated with weekly bisphosphonates. ----- METHODS: HR-QoL was assessed by Euroqol (EQ-5D) and Osteoporosis Targeted Quality of Life (OPTQoL) questionnaires. ----- RESULTS: The EQ-5D questionnaire showed significant improvement associated with ibandronate treatment, occurring in mobility (p < 0.01), usual activity (p < 0.01), pain/discomfort (p < 0.05), and anxiety/depression (p < 0.05). In addition, ibandronate treatment considerably improved patients' perceived health on a visual analog scale (p < 0.001). For the OPTQoL questionnaire, patients reported less physical difficulty (p < 0.001), fewer adaptations in their lives (p < 0.001), and less fear (p < 0.001) with ibandronate than with weekly bisphosphonates. ----- CONCLUSION: The study demonstrated that patients who were transferred from weekly bisphosphonates to a monthly ibandronate experienced improved HR-QoL

Which clinical variables have the most significant correlation with quality of life evaluated by SF-36 survey in Croatian cohort of patient with ankylosing spondylitis and psoriatic arthritis?

The aim of our study was to assess clinical variables with the best correlation to quality of life (QOL) assessed by medical outcome survey Short-Form 36 (SF-36) in patients with spondyloarthritides, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA). We analyzed the cohort of 54 patients (22 patients with PsA and 32 patients with AS), who filled the Croatian version of SF-36. For each type of arthritis, patients were clinically evaluated using the extensive list of clinical variables categorized into subjective and objective group. For AS patients, subjective and objective variables (spinal mobility measurements, clinical assessment of spinal pain, patient assessments of disease activity and pain) correlated mainly with the physical functioning concept of SF-36. Patients assessments of fatigue correlated with the energy/fatigue subscale, whereas patient assessment of enthesial pain correlated with the pain subscale. Correlations between clinical variables and SF-36 concepts of PsA patients showed more diverse distribution than for AS. Objective variables (spinal mobility measurements, a 76-joint score, clinical assessment of spinal pain) correlated with concepts concerning physical health and pain. Several subjective patient assessments correlated with energy/fatigue, emotional well-being, pain and general health subscales. Both patient and physician assessment of PsA activity correlated with the role limitations due to emotional problems. Bath ankylosing spondylitis functional index (BASFI) had the strongest correlation with the physical functioning concept of SF-36 in both diseases. Our findings provide important information to help selecting the variables with strongest impact on QOL, for better planning the management strategies and achieving better rehabilitation results

Campus virtuales : revista científica iberoamericana de tecnología educativa

Resumen basado en el de la publicaciónResumen en inglésSe describe la creación y contenidos de una plataforma de e-learning llamada AprendeBn para el sistema educativo panameño. Se comienza realizando un análisis de la problemática educativa en Panamá a partir de los informes del Ministerio de Educación (MEDUCA). Posteriormente se hace una evaluación comparativa de las principales plataformas de este tipo y se describen las características más relevantes de cada una de ella. Se pretende desarrollar una plataforma para Panamá que se enfoca en el estudiante y educador panameño de los niveles de premedia y media. En la plataforma se utiliza el formato, las mejores ideas y la experiencia de otras de similares características pero teniendo en cuenta los factores locales y los objetivos del sistema educativo panameño. Se persigue contar con un recurso tecnológico y social educativo, donde tanto estudiantes como educadores cuenten con contenidos actualizados de los programas oficialesES

Additional file 1: Figure S1. of Chemokine signals are crucial for enhanced homing and differentiation of circulating osteoclast progenitor cells

Increased frequency of osteoclast progenitor cells and subsets expressing chemokine receptors in peripheral blood and synovial fluid samples of patients with RA and PsA. a Proportion of OCPs, subsets expressing macrophage colony-stimulating factor receptor (CD115) and RANK in peripheral blood of CTRL subjects and patients with arthritis, and SF samples (SF RA, SF PsA), assessed by flow cytometry. b Concentrations of soluble RANKL in SF of arthritic patients, measured by ELISA. c Chemokine receptor expression on OCPs in peripheral blood of CTRL subjects and patients with arthritis, and SF of patients with arthritis, assessed by flow cytometry. Values are presented as medians (middle line), with boxes representing IQR, whiskers representing 1.5 times the IQR, and squares or circles representing outliers. Group-to-group comparisons were performed using a nonparametric Mann-Whitney U test, and p values <0.05 are shown for comparisons made between PsA and other groups. Previously shown p values for comparisons between RA and CTRL groups (Figs. 2 and 3) are not shown again for the sake of visual clarity. (TIF 1768 kb