The human prostaglandin E2 (PGE2) receptor EP4 (or PTGER4) is abundantly expressed. Activation of EP4 receptor induces osteoblasts and thereby stimulates de novo bone formation. Results from targeted deletion of the EP4 receptor also suggest that the EP4 subtype of the PGE2 receptor is involved in lipopolysaccharide-induced bone resorption. Modulating EP4 action may thus prove to be clinically useful for the treatment of bacterially induced bone loss, such as in periodontitis and osteomyelitis. EP4 also plays a role in the anti-inflammatory action of PGE2 in human macrophage.