Bone biomechanical properties in prostaglandin EP 1 and EP 2 knockout mice

Abstract

Prostaglandins play an important role in regulating the bone adaptation response to mechanical stimuli. Prostaglandin E2 (PGE 2) is an effective modulator of bone metabolism. Administration of PGE 2 to rodents results in increased cancellous and cortical bone mass translating into enhanced mechanical strength. The PGE 2 influence on bone is mediated through four well-characterized receptors (EP 1, EP 2, EP 3, and EP 4). Although the PGE 2 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 regulating PGE 2-related bone cell function. The EP 1 subtype is coupled with Ca 2+ mobilization. The EP 2 subtype stimulates cyclic adenosine monophosphate (cAMP) formation. cAMP in turn is responsible for the early cellular signal that stimulates bone formation. This study compared physical and biomechanical properties of bone in EP 1 and EP 2 knockout mice to their corresponding wild-type controls. Ash weight was measured in the ulnae, and femurs and vertebral bodies were tested in three-point bending and compression, respectively. The results suggest: (a) EP 1 receptors have a minimal influence on skeletal strength or size in mice; and (b) EP 2 receptors have a major influence on the biomechanical properties of bone in mice. The absence of EP 2 receptors resulted in weak bone biomechanical strength properties in the EP 2 knockout model as compared with the corresponding wild-type control mice.