Olga Addimanda

WNT16 antagonises excessive canonical WNT activation and protects cartilage in osteoarthritis.

Objective Both excessive and insufficient activation of WNT signalling results in cartilage breakdown and osteoarthritis. WNT16 is upregulated in the articular cartilage following injury and in osteoarthritis. Here, we investigate the function of WNT16 in osteoarthritis and the downstream molecular mechanisms. Methods Osteoarthritis was induced by destabilisation of the medial meniscus in wild-type and WNT16-deficient mice. Molecular mechanisms and downstream effects were studied in vitro and in vivo in primary cartilage progenitor cells and primary chondrocytes. The pathway downstream of WNT16 was studied in primary chondrocytes and using the axis duplication assay in Xenopus. Results WNT16-deficient mice developed more severe osteoarthritis with reduced expression of lubricin and increased chondrocyte apoptosis. WNT16 supported the phenotype of cartilage superficial-zone progenitor cells and lubricin expression. Increased osteoarthritis in WNT16-deficient mice was associated with excessive activation of canonical WNT signalling. In vitro, high doses of WNT16 weakly activated canonical WNT signalling, but, in co-stimulation experiments, WNT16 reduced the capacity of WNT3a to activate the canonical WNT pathway. In vivo, WNT16 rescued the WNT8-induced primary axis duplication in Xenopus embryos. Conclusions In osteoarthritis, WNT16 maintains a balanced canonical WNT signalling and prevents detrimental excessive activation, thereby supporting the homeostasis of progenitor cells.

Can adipokines serum levels be used as biomarkers of hand osteoarthritis

Abstract Purpose: To evaluate serum levels of visfatin, resistin and adiponectin in patients with erosive (E) and non-erosive (NE) osteoarthritis (OA) of the hand (HOA) compared to normal controls (NC). Methods: 94 outpatients with E HOA and NE HOA and 21 NC were enrolled. The radiological assessment of both hands was performed according to the Kellgren–Lawrence and Kallman score. Patients were divided into two subsets (lone HOA or generalized OA) based on clinically OA involvement of knee and hip. Serum visfatin, resistin and adiponectin levels were determined by ELISA assay. Results: Visfatin was significantly higher in E HOA patients in comparison to NC and NE HOA group. Resistin showed a significant increase in both E HOA and NE HOA groups versus NC, in particular in generalized OA. No significant differences among groups were found in adiponectin. The Kallman score was more severe in the two subsets of E HOA patients compared to NE HOA. Conclusions: This study showed increased levels of resistin in erosive and non-erosive HOA, and higher visfatin levels in E HOA in comparison to NE HOA. These data suggest the adipokines possible role in the pathogenesis of HOA and their potential usefulness as biomarkers of the disease.

Predictors of Loss of Remission and Disease Flares in Patients with Axial Spondyloarthritis Receiving Antitumor Necrosis Factor Treatment: A Retrospective Study

Objective. The aim of this study was to evaluate rate and predictive factors of loss of remission and disease flare in patients with axial spondyloarthritis (axSpA) receiving antitumor necrosis factor (anti-TNF) treatment. Methods. In this retrospective multicenter study, patients with axSpA, according to the Assessment of Spondyloarthritis international Society (ASAS) criteria, treated with adalimumab, etanercept, or infliximab with a minimum followup of 12 months and satisfying the ASAS partial remission criteria and/or Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease were studied. Disease flare was defined as a Bath Ankylosing Spondylitis Disease Activity Index score > 4.5 or ASDAS score > 2.5 on at least 1 occasion. Results. One hundred seventy-four patients with axSpA were studied. After a median [interquartile range (IQR)] followup of 4 years (2–6), 37 patients (21.2%) experienced a loss of remission and 28 (16.1% of the whole study group) a disease flare. Median (IQR) duration of remission in patients who lost this status was 1 year (0.625–2). Higher median erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values, continuous nonsteroidal antiinflammatory drug (NSAID) use, and an ASDAS-CRP ≥ 0.8 during the remission period were significantly associated with both loss of remission and disease flare. At the multivariate analysis, continuous NSAID intake (OR 4.05, 95% CI 1.4–11.74, p = 0.010) and ESR > 15 (OR 2.90, 95% CI 1.23–6.82, p = 0.015) were the only factors predictive of disease reactivation. Conclusion. In this study, loss of remission and disease flares occurred, respectively, in about 21% and 16% of the patients with axSpA who achieved a state of remission while receiving anti-TNF therapy. Residual disease activity was associated with disease reactivation.

The Sex Influence on Response to Tumor Necrosis Factor-α Inhibitors and Remission in Axial Spondyloarthritis

Objective. The aim of this study was to evaluate the influence of sex on response to treatment and disease remission in patients with axial spondyloarthritis (axSpA). Methods. In this retrospective multicenter study, patients with axSpA, according to the Assessment of Spondyloarthritis international Society (ASAS) criteria for axSpA, and treated with adalimumab, etanercept, golimumab, or infliximab, were studied. We compared clinical characteristics, patient-reported outcomes, disease activity, function, and response to treatment in male and female patients with this disease. Results. Three hundred forty patients with axSpA (270 with ankylosing spondylitis, 19 with psoriatic arthritis with axial involvement, and 51 with nonradiographic axSpA) were studied. Male subjects had a significantly higher prevalence of grade IV sacroiliitis, higher levels of serum C-reactive protein, lower Maastricht Ankylosing Spondylitis Enthesitis Score, and fatigue when compared with females. Further, Kaplan-Meier survival curves showed that the rate of partial remission, ASAS40 response, and Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement, but not ASDAS inactive disease, were significantly lower in female patients. Conclusion. Our data suggest that female sex was associated with a lower rate of response to treatment and of disease remission in patients with axSpA treated with antitumor necrosis factor-α drugs.

Could myeloperoxidase represent a useful biomarker for erosive osteoarthritis of the hand

Erosive osteoarthritis of the hand (EHOA) represents a subset of osteoarthritis of the hand (HOA) that affects proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints. EHOA is characterized by acute onset, severe pain, functional limitation, and tissue swelling; it is generally recognized by radiographic central erosion with collapse of the subchondral bone and a so-called ‘gull-wing’ or ‘saw-tooth’ deformity (1, 2). Despite the presence of inflammatory symptoms and signs, laboratory findings are usually negative; controversial data have been reported about erythrocyte sedimentation rate and high-sensitivity C-reactive protein (hs-CRP) (3). In a previous study, Punzi et al. demonstrated increases in myeloperoxidase (MPO) and in the nitrated form of type II collagen-derived fragments (Coll2-1NO2) in EHOA in comparison to non-erosive osteoarthritis of the hand (NEHOA) (4). The objective of the present study was to investigate the serum levels of MPO and hs-CRP and their possible relationship with the clinical and radiological findings in patients with EHOA and NEHOA. A total of 135 consecutive outpatients with HOA according to the American College of Rheumatology criteria (5) were enrolled in this study. We excluded subjects with other rheumatic diseases and those with a personal and/or familial history of psoriasis. All patients were examined by anteroposterior X-ray projection of both hands; EHOA was defined by the presence of at least one central erosion in PIP or DIP. On the basis of these criteria, 80 patients were included in the EHOA group and 55 in the NEHOA group. Twenty-five healthy subjects without finger joint pain and/or tenderness or finger nodes were considered as controls. Radiological evaluation was performed by two experimented readers according to the Kallman grading scale (6). All subjects signed an informed consent form and the study was approved by the local ethics committees. Human hs-CRP was detected by CircuLex high-sensitivity CRP enzyme-linked immunosorbent assay (ELISA) (CycLex Co., Nagano, Japan) according to the user’s manual. The limit of detection of samples was 28.6 pg/mL. Serum MPO was measured by human MPO ELISA (BioVendor, Heidelberg, Germany) and followed the manufacturer’s instructions. The sensitivity of the assay was 0.4 ng/mL. The Mann–Whitney U-test and analysis of covariance (ANCOVA) were used for comparisons among groups.