The NF-κB signalling pathway in osteoarthritis

Nuclear factor-kappaB (NF-κB) proteins constitute a family of transcription factors that are stimulated by pro-inflammatory cytokines, chemokines, stress-related factors and extracellular matrix (ECM) degradation products. Upon stimulation, the activated NF-κB molecules trigger the expression of an array of genes which induce destruction of the articular joint, leading to osteoarthritis (OA) onset and progression. Therefore, targeted strategies that interfere with NF-κB signalling could offer novel potential therapeutic options for OA treatment. In this review, we discuss the involvement of NF-κB in OA pathogenesis and how pharmacological inhibition of the NF-κB signalling pathway affects OA incidence and evolution. © 2013 Elsevier Inc. All rights reserved

Association of rs1568885, rs1813443 and rs4411591 polymorphisms with anti-TNF medication response in Greek patients with Crohn's disease

AIM: To investigate the correlation between rs1568885, rs1813443 and rs4411591 polymorphisms and response to infliximab in a cohort of Greek patients with Crohn's disease (CD). METHODS: One hundred and twenty-six patients diagnosed with CD based on standard clinical, endoscopic, radiological, and pathological criteria were enrolled in this study at the Gastroenterology Unit of the 2nd Department of Surgery and at the Colorectal Unit of the 1st Department of Propaedeutic Surgery. Infliximab at a dose of 5 mg/kg was administered intravenously at weeks 0, 2, 6 and then every 8 wk. Clinical and serological responses were assessed using the Harvey-Bradshaw Index and serum C-reactive protein (CRP) levels, respectively, and the endoscopic response was evaluated by ileocolonoscopy performed at baseline and after 12-20 wk of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and non-responders. Genomic DNA from whole peripheral blood was extracted and genotyping was performed by allele-specific polymerase chain reactions. χ2 test with Yate's correction based on the S-Plus was used to compare the genotype frequencies. RESULTS: Eighty patients (63.49%) were classified as complete and 32 (25.39%) as partial responders to infliximab, while 14 (11.11%) were primary non-responders. No correlation was found between response to infliximab and patients' characteristics such as age, gender and disease duration. There was consistency between Harvey-Bradshaw index scores and serum CRP levels. The TT genotype of the rs1568885 polymorphism was significantly related to partial response (P = 0.024) and resistance to infliximab (P = 0.007) while the AT genotype was more frequent in partial responders (P = 0.035) and in primary non-responders (P = 0.032). Regarding rs1813443, the CC genotype was found to be associated with partial response (P = 0.005) and primary resistance (P = 0.002) to infliximab while no association was found between the rs4411591 polymorphism and the clinical response to infliximab. CONCLUSION: Based on our results, the rs1568885 and rs1813443 polymorphisms are associated with clinical and biochemical response to infliximab in Greek patients with Crohn's disease. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved