TLR4 and Hyperinsulinemia: Recently, insulin was shown to inhibit TNFα‐induced OA‐related catabolic genes in fibroblast‐like synoviocytes from OA joints; therefore, it is possible that hyperinsulinemia seen in control‐diet DAP12 KO mice may provide some aged‐related OA protection that we observed.29 Thus, changes in glucose homeostasis alone do not explain the protection from HFD‐induced OA in TLR4 KO mice and the acceleration of HFD‐induced cartilage catabolism seen in DAP12 KO aged female mice.