lewis-x-antigen and Osteoarthritis

Osteoarthritis (OA) is the most common joint disease, characterized by articular cartilage degradation and changes in all other joint tissues. MicroRNAs (miRNAs) play an important role in mediating the main risk factors for OA. This study aimed to investigate the effect of miR-26a/26b on the proliferation and apoptosis of human chondrocytes by targeting fucosyltransferase 4 (FUT4) through NF-κB signaling pathway. We revealed the differential expression profiles of FUT4 and miR-26a/26b in the articular cartilage tissues of OA patients and normal people. The ability of miR-26a/26b to specifically interact with the 3'UTR of FUT4 was demonstrated via a luciferase reporter assay in chondrocytes. Further results showed altered levels of miR-26a/26b and FUT4 could regulate the process of IL-1β-induced extracellular matrix degradation in chondrocytes. Forced miR-26a/26b expression was able to affect chondrocytes proliferation and apoptosis, while altered expression of FUT4 in chondrocytes modulated progression upon transfection with miR-26a/26b mimic or inhibitor. In OA mice, the overexpression of miR-26a/26b by intra-articular injection significantly attenuated OA progression. In addition, regulating FUT4 expression markedly modulated the activity of NF-κB signaling pathway, and this effect could be reversed by miR-26a/26b. In short, miR-26a/-26b/FUT4/NF-κB axis may serve as a predictive biomarker and a potential therapeutic target in OA treatment.

Topics: 3' Untranslated Regions; Animals; Apoptosis; Cartilage, Articular; Cell Proliferation; Cells, Cultured; Chondrocytes; Disease Progression; Enzyme Repression; Fucosyltransferases; Genes, Reporter; Humans; Injections, Intra-Articular; Interleukin-1beta; Lewis X Antigen; Male; MicroRNAs; NF-kappa B; Osteoarthritis; Rats, Sprague-Dawley; RNA; RNA Interference; RNA Isoforms; Signal Transduction

Immunohistochemical synovial tissue biomarkers are used increasingly to classify arthropathies, study their pathogenesis, and to measure disease activity in clinical trials. We have used receiver operating characteristic (ROC) analysis to quantify the discriminatory abilities of markers for common inflammatory cells (subintimal CD15, CD68, CD3, CD20, CD38, and lining CD68), proliferating cells (Ki-67) and blood vessels (von Willebrand factor, vWF) among inflammatory (chronic septic arthritis, early arthritis and rheumatoid arthritis (RA)) and degenerative arthropathies (osteoarthritis (OA) and orthopedic arthropathies) and normal synovium. Six of the eight markers distinguished accurately between RA and the degenerative arthropathies (area under the curve (AUC) 0.91-0.97), whereas subintimal CD68 (AUC 0.92) and Ki-67 (AUC 0.87) distinguished best between OA and normal synovium. Fold differences in mean expression correlated only modestly with AUCs (r(2) = 0.44). Multicategory ROC analysis ranked Ki-67, subintimal CD68, and CD15 as discriminating best among all six sample groups, and thus identified them as the most broadly applicable markers.

Topics: Antigens, CD; Antigens, CD20; Antigens, Differentiation, Myelomonocytic; Area Under Curve; Arthritis, Infectious; Arthritis, Rheumatoid; Biomarkers; CD3 Complex; Humans; Ki-67 Antigen; Lewis X Antigen; Osteoarthritis; ROC Curve; Synovial Membrane; Synovitis; von Willebrand Factor

To analyze the differentiation stages of myeloids statistically, we adopted a two-color FACS system and used appropriate monoclonal antibodies belonging to CD15, CD16 and CD11b. By using HL60 treated with DMSO or human bone marrow MNCs from patients with rheumatoid arthritis, it was proved that with this system, myeloids could be clearly separated according to differentiation stages. Furthermore, the number of myeloids at certain stages of differentiation in the epiphyseal bone marrow of patients with RA or OA was measured. Nine of 15 samples from RA patients showed immature and relatively mature myeloids, while none of the 8 OA samples did. When the proportions of myeloids in epiphyseal bone marrow MNCs were compared with the clinical features, disease subsets in RA and the degree of synovitis, seemed to be important factors for abnormal myelopoiesis.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, Differentiation; Arthritis, Rheumatoid; Bone Marrow; CD11 Antigens; Cell Differentiation; Dimethyl Sulfoxide; Female; Flow Cytometry; Growth Plate; Humans; Joints; Leukemia, Myeloid, Acute; Lewis X Antigen; Male; Middle Aged; Osteoarthritis; Receptors, Fc; Receptors, IgG; Tumor Cells, Cultured