Antibiotic Treatment Prior to Injury Abrogates the Detrimental Effects of LPS in Mice Susceptible to Osteoarthritis Development.

Post traumatic osteoarthritis (PTOA) is a form of secondary osteoarthritis (OA) that develops in ~50% of cases of severe articular joint injuries and leads to chronic and progressive degradation of articular cartilage and other joint tissues. PTOA progression can be exacerbated by repeated injury and systemic inflammation. Few studies have examined approaches for blunting or slowing down PTOA progression with emphasis on systemic inflammation; most arthritis studies focused on the immune system have been in the context of rheumatoid arthritis. To examine how the gut microbiome affects systemic inflammation during PTOA development, we used a chronic antibiotic treatment regimen starting at weaning for 6 weeks before anterior cruciate ligament (ACL) rupture in mice combined with lipopolysaccharide (LPS)-induced systemic inflammation. mice develop spontaneous OA as well as a more severe PTOA phenotype than mice. By 6 weeks post injury, histological examination showed a more robust cartilage staining in the antibiotic-treated (AB) mice than in the untreated controls. Furthermore, we also examined the effects of AB treatment on systemic inflammation and found that the effects of LPS administration before injury are also blunted by AB treatment in mice. The AB- or AB+LPS-treated injured joints more closely resembled the VEH OA phenotypes than the vehicle- or LPS-treated , suggesting that antibiotic treatment has the potential to slow disease progression and should be further explored therapeutically as prophylactic post injury. © 2023 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.