Possible immune mechanisms initiated by 7-ketocholesterol that contribute to synovial oxidative stress and inflammation

Osteoarthritis (OA) is a chronic joint disease caused by both mechanical damage and metabolic factors, which intertwine in their pathogenetic pathways. We hypothesise that the oxidised cholesterol derivative, 7-ketocholesterol (7-KCh), represents a danger signal in the synovia of patients with OA and promotes low-grade inflammation. The study would aim to elucidate the possible immune mechanisms initiated by 7-KCh that contribute to oxidative stress and inflammation in the synovia and synovial CD68+ cells, which are mostly macrophages. The polarisation of synovial CD68+ cells, their tissue distribution in relation to T and natural killer (NK) cells, and the influence of 7-KCh on the phenotype and intracellular cytokine and chemokine production in suspension is worth analysing. We envisage that this research would contribute to a better understanding of the biology of CD68+ macrophages influenced by 7-KCh and encourage the development of therapeutic approaches based on directing macrophage polarisation.