Knee osteoarthritis (OA)-related phenotypes of myeloid-derived suppressor cells (MDSCs) is mediated by infrapatellar fat pat (IPFP)-derived factors in a body mass index (BMI)-dependent manner and positively correlates with IPFP-derived adiponectin le

Osteoarthritis (OA) is characterized by cartilage destruction and immune cell infiltration, of which include myeloid-derived suppressor cells (MDSCs). MDSCs have been shown to expand in obese patients with OA. Therefore, we aimed to investigate the role of obesity on MDSC function in knee OA patients. We isolated MDSCs from infrapatellar fat pads (IPFPs) of knee OA patients and evaluated MDSCs both quantitatively and qualitatively. We also performed a transcriptomic analysis of IPFP-isolated MDSCs of low, moderate and high body mass index (BMI) patients. In vitro IPFP-cultured media (CM)- and/or synovial tissues (ST)-CM-treated monocyte-derived MDSCs were evaluated for gene expression, immunosuppressive function and osteoclastogenesis potential. Cytokine and adipokine screening of IPFP-CM and ST-CM used for treatment were also screened. MDSC abundance and cytokine expression correlated with increasing BMI. Transcriptomic analysis revealed upregulation of numerous genes in OA-related pathways in IPFP-isolated MDSCs of moderate and high BMI patients, but downregulated in low BMI patients. In vitro assays demonstrate upregulation of OA-related genes, increased cytokine production, impaired immunosuppressive function and increased osteoclastogenesis potential of monocyte-derived MDSCs in a BMI-dependent manner, predominantly from IPFP-CM. IPFP-derived adiponectin levels correlated significantly with BMI status; interleukin (IL)-1β, MCP1, IL-17A, IL-12p70, and IL-8 levels that were secreted from monocyte-derived MDSCs in response to IPFP-CM treatment; and immunosuppressive function. Obesity may be driving knee OA pathology via metabolic changes in IPFPs. These changes directly and indirectly affect MDSC phenotype and function, of which include phenotypes that favor OA pathology.