Alterações fenotípicas dos glicosaminoglicanos provenientes de cartilagem osteoartrítica induzem aumento de il-1β e il-17 in vivo e il-1β in vitro, um possível biomarcador para a osteoartrite

Abstract

Osteoarthritis (OA) is a chronic degenerative disease where there seems to be an imbalance between the synthesis and degradation of the articular cartilage. It is associated with chronic pain and functional disability. However, the manifestation of these two signs characterizes a chronic and advanced, since in humans, the lack of objective and reliable methods to evaluate the evolution of OA limits its clinical study. The difficulties include tissue unavailability for histopathological analysis, particularly in the early stages of the disease, absence of reliable biological markers, and unconventional standardization in imaging methods. Taking into account that chondroitin sulfate (CS) is the predominant glycosaminoglycan (GAG) in cartilage. In addition, changes in the amount and molecular weight have already been demonstrated in previous animal and human studies, so we decided to investigate the types of molecular changes in the patients and whether this was related to the change in inflammatory potential, since the characterization of these modifications could be a biomarkers of OA. GAGs of patients submitted to OA arthroplasty or fracture were isolated by enzymatic proteolysis, quantified, analyzed for molar and elemental mass, and electrical charge, and then were administered (50 μg / mL) intra-articular (ia) in mice, (IL-1, IL-1, IL-1, IL-1, IL-1 and IL-1) IL-5, IL-6, IL-10, IL-17, CXCL-1, γ-INF and TNF-α); * = p <0.01 and nd (undetected). Migration was still evaluated after 7 days. The relative motility and molar mass of CS from humans with OA do not differ as compared to the fracture group, as they are not altered by gender, nor does the molar mass of CS be altered by age. However, OA reduces sulfur and negative charge percentages in GAGs when compared to the fracture group, as well as the genus reduces sulfur percentages. GAG i.a from patients with or without OA induces acute cellular inflow. However, they do not differ in terms of acute, chronic or acute cellular influx, but in synovitis. Already the acute cellular influx is altered by gender. GAG i.a from patients with or without OA induces the release of cytokines, such as IL-6, IL-17, TNF-α, INF-Y, CXCL-1, IL-1β and IL-10. However, OA significantly increases levels of IL-1β and IL-17, as well as the fracture group significantly increases the levels of INF-Y and IL-10 in synovial fluid, and iNOS immunoexpression in synovium. Yet the release of cytokines induced by GAGs is not altered by gender. In vitro, GAG induces the release of IL-6 in vitro. However, only GAGs from patients with OA significantly increase IL-1β levels. This is the first description that GAGs undergo elemental and negative charge reductions. In addition, they promote cytokine release, whose profile differs in samples from patients with and without OA. In vivo release is greater and more diverse than in vitro. The difference in the cytokine profile between cartilage GAG ​​of patients with and without OA influences the definition of biomarkers, an unmet need in the handling of this disease.