Osteoarthritis induced by destabilization of the medial meniscus is reduced in germ-free mice

Summary Objective To determine the contribution of the gut microbiota to the development of injury-induced osteoarthritis (OA). Design OA was induced using the destabilized medial meniscus (DMM) model in 20 germ-free (GF) C57BL/6J male mice housed in a gnotobiotic facility and 23 strain-matched specific pathogen free (SPF) mice in 2 age groups -13.5 weeks avg age at DMM (17 SPF and 15 GF) and 43 weeks avg age at DMM (6 SPF and 5 GF). OA severity was measured using scores for articular cartilage structure (ACS), loss of safranin O (SafO) staining, osteophyte size, and synovial hyperplasia. Microbiome analysis by 16S rRNA amplicon sequencing was performed on stool samples and LPS and LPS binding protein (LBP) were measured in plasma. Results Compared to the SPF DMM mice, the maximum (MAX) ACS score per joint was 28% lower (p =0.036) in GF DMM mice while the SafO sum score of all sections evaluated per joint was decreased by 31% (p=0.009). The differences between SPF and GF mice in these scores were greater when only the younger mice were included in the analysis. The younger GF DMM mice also had significant reductions in osteophyte size (36%, p=0.0119) and LBP (27%, p=0.007) but not synovial scores or LPS. Differences in relative abundance of a number of Operational Taxonomic Units (OTUs) were noted between SPF mice with high vs. low maximum ACS scores. Conclusions These results suggest factors related to the gut microbiota promote the development of OA after joint injury.