Here, using two genetically engineered mouse models, we show that osteocytes/osteoblasts produce and secrete SAA3 due to the loss of TSC1 and reduces CYP7A1 expression in hepatocytes through TLR4‐c‐Jun signaling axis, thus impeding hepatic cholesterol catabolism and resulting in hypercholesterolaemia. The gene discussed is TLR4; the disease is Hypercholesterolemia.