Effect of dietary components on arthritis and bone remodeling

Abstract

Inflammation is an immune response that aims to protect the body against antigens and maintain the state of homeostasis. Consequently, this response leads to mobilization of metabolic substrates to generate an adequate support for it. Thus, both the inflammatory response interferes in intermediary metabolism as the nutritional status of the individual interferes with the inflammatory response. The first aim of this thesis was to evaluate the impact of acute joint inflammation on metabolism. Moreover, it was also aimed to determine whether the consumption of diets that alter the adipose tissue mass influences the inflammatory response. Acute joint inflammation in the knee of mice led to metabolic alterations. The use of inhibitor of cytokine instead of neutrophils appears to be a better alternative to improve thesemetabolic changes. On the other hand, chronic metabolic alterations induced by different dietary compositions altered the inflammatory response in the knee after challenge with antigen-induced joint inflammation. Together, we demonstrated that acute inflammation alters the metabolism. However, animals with metabolic abnormalities present joint inflammation attenuated. The second aim of this thesis was to analyze the effect of bovine-milk extracellular vesicles (BMEVs) on chronicarthritis and bone remodeling. BMEVs were caracterized by nanoparticle presence sized <220nm containing mRNA, miRNA, and proteins. In experimental chronic arthritis, it was shown that BMEVs are interesting nano/microparticle-based therapeutic agents to treat arthritis since reduce pro-inflammatory mediators and also attenuate the symptoms of the disease, although their in vivo mode of action remains to be elucidated. Thus, based on evidences in literature and our results, we also hypothesized that BMEVs could be used as tool for therapy of patients with arthritis. On the other hand, milk consumption is highly associated with bone formation, however it is still a controversial issue. BMEVs could interfere in the bone homeostasis, which is an orchestrated process between osteoclasts, osteoblasts and osteocytes. The fact that osteoblast differentiation is accelerated into osteocytes by BMEVs appears to influence dramatically the bone matrix leading to woven boneformation, which is more brittle and more vulnerable for fracture if not replaced by lamellar bone. Also, there was an increase in the differentiation of small osteoclasts, their activity was impaired and appeared to be related to a reduction in acid secretion. It was showed that nanoparticles in milk are modulators of immunity and bone by regulating arthritis response, osteoblast and osteoclast differentiation.Therefore, we demonstrated how dietary components may influence states of health and disease and this is important to create future strategies of therapies related to arthritis and bone.