Bone biomechanical properties in prostaglandin EP1 and EP2 knockout mice

Prostaglandins play an important role in regulating the bone adaptation res ponse to mechanical stimuli. Prostaglandin E2 (PGE(2)) is an effective modu lator of bone metabolism. Administration of PGE2 to rodents results in incr eased cancellous and cortical bone mass translating into enhanced, mechanic al strength. The PGE2 influence on bone is mediated through four well-chara cterized receptors (EP1, EP2, EP3, and EP,). Although the PGE2 pathways and mechanisms of action on cells involved in bone adaptation are still under investigation, it is now known that each receptor plays a unique role in re gulating PGE(2)-related bone cell function. The EP1 subtype is coupled with Ca2+ mobilization. The EP2 subtype stimulates cyclic adenosine monophospha te (cAMP) formation. cAMP in turn is responsible for the early cellular sig nal that stimulates bone formation. This study compared physical and biomec hanical properties of bone in EP1 and EP2 knockout mice to their correspond ing wild-type controls. Ash weight was measured in the ulnae, and femurs an d vertebral bodies were tested in three-point bending and compression, resp ectively. The results suggest: (a) EP1 receptors have a minimal influence o n skeletal strength or size in mice; and (b) EP2 receptors have a major inf luence on the biomechanical properties of bone in mice. The absence of EP2 receptors resulted in weak bone biomechanical strength properties in the EP 2 knockout model as compared with the corresponding wild-type control mice. (C) 2001 by Elsevier Science Inc. All rights reserved.