Role of selenium in articular cartilage metabolism, growth and maturation

Abstract : In China, a severe musculoskeletal disease called Kashin-Beck disease (KBD) is largely endemic over a large geographical area. It has been reported that more than 2.5 million people in China suffer from KBD and about 30 million people are at risk. Geological and epidemiological investigations have shown that a strong correlation exists between the location of selenium (Se) deficient soils and the distribution of KBD in the population. The disease is manifested as degradation of the matrix, cell necrosis mainly in the articular and growth plate cartilage, which can result in growth retardation, secondary osteoarthrosis, and disability in daily life. The worst forms of this disease tend to start in childhood, which may lead to dwarfism. Selenium is present everywhere in the environment (water, air, soils) and it is mainly incorporated to the human organism through the daily diet (water, cereals). Although this trace nutriment element is essential for normal cellular function. Most of the selenium-related -functions and pathways remain incompletely understood. Whilst vital for normal function, it is toxic at concentration slightly higher than that required by the body. Consequently, it is present within the organism in parts per billion (microgram per liter) making it difficult to localize and analyze its role in metabolism. Despite being a trace element it is an essential component of antioxidant and anti-inflammatory-related proteins that protect cells against oxidative attack. Furthermore, several studies have exposed the role selenium plays in tissue development such as in articular cartilage. This action seems to be mediated via selenoproteins that are indirectly involved in normal cartilage growth and homeostasis. In the USA, a clinical study has shown strong evidence that Se-deficiency influences cartilage metabolism inducing a favorable environment for the onset and the progression of osteoarthritis. Even if the selenium is not the only factor in the development of degenerative joint disease, it is highly likely that its absence impacts its growth and development of articular cartilage. The main focus of this study was then to understand better the role of Se in the normal metabolic processes of articular cartilage. Cultures of articular cartilage explants were used on a previously validated in vitro model of tissue maturation to analyze the role of selenium in growth and development. Physical and chemical experiments were preformed to understand how the presence of selenium affects tissue organization. It has been possible to determine a fundamental recurrent pattern of Se-distribution in the tissue. It appears to be localized at cell-matrix interfaces and it can be hypothesized that Se plays role in cell signaling or mechanotransduction. Biomechanical, structural and molecular analyses have been made to characterize the extracellular matrix of articular cartilage treated with different concentrations of Se-level. We discovered that Se-deficiency induces morphological changes in the cartilage matrix during the fast maturation-like process, which could be related to degenerative-like morphology of the cartilage. This could potentially be associated with degenerative changes that occur in KBD patient during childhood. This project is a prospective work for a potential future enhancement of the regenerative or preventive treatments for specific musculoskeletal diseases with a metabolic component.
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Caroline Bissardon. Role of selenium in articular cartilage metabolism, growth and maturation. Toxicology. Université Grenoble Alpes, 2016. English. ⟨NNT : 2016GREAU013⟩. ⟨tel-01942169⟩

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