Intra-Articular Lipopolysaccharides Are Not Driving the Progression of Osteoarthritis

Purpose: Osteoarthritis (OA) is a complex multi-tissue disease of the joint characterized by low grade chronic inflammation and mechanical erosion of cartilage. One of the main risk factors for OA is obesity that is linked to an imbalanced gut microbiota. Under these conditions, the gut epithelium may become permeable which leads to translocation of molecules such as lipopolysaccharides (LPS) from the gastrointestinal tract to the circulatory system. LPS is part of the outer membrane of Gram-negative bacteria that has been found in the synovial fluid of OA patients. Studies have previously correlated levels of LPS in serum, synovial tissue and synovial fluid with OA severity. LPS is a powerful mediator of systemic inflammation and a driver of septic shock syndrome. It induces multiple inflammatory pathways, as it stimulates toll-like receptors such as TLR4 and TLR2 through which it activates nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFkB). However, it's role in progression of OA is currently unknown. The goal of the study was to elucidate the role of intra-articular LPS in OA.