Bone biomechanical properties in prostaglandin EP1 and EP2 knockout mice.
Prostaglandins play an important role in regulating the bone adaptation response to mechanical stimuli. Prostaglandin E2 (PGE2) is an effective modulator of bone metabolism. Administration of PGE2 to rodents results in increased cancellous and cortical bone mass translating into enhanced mechanical strength. The PGE2 influence on bone is mediated through four well-characterized receptors (EP1, EP2, EP3, and EP4). 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 regulating PGE2-related bone cell function. The EP1 subtype is coupled with Ca2+ mobilization. The EP2 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 EP1 and EP2 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) EP1 receptors have a minimal influence on skeletal strength or size in mice; and (b) EP2 receptors have a major influence on the biomechanical properties of bone in mice. The absence of EP2 receptors resulted in weak bone biomechanical strength properties in the EP2 knockout model as compared with the corresponding wild-type control mice.
Akhter
M P
MP
Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA.
Cullen
D M
DM
Gong
G
G
Recker
R R
RR
D000818:Animals; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000033:anatomy & histology / Q000502:physiology*; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype
C545636:Ptger1 protein, mouse; C545645:Ptger2 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D000242:Cyclic AMP