title: Loss of the PGE2 receptor EP1 enhances bone acquisition, which protects against age and ovariectomy-induced impairments in bone strength.
abstract: PGE2 exerts anabolic and catabolic effects on bone through the discrete actions of four prostanoid receptors (EP1-4). We have previously demonstrated that loss EP1 accelerates fracture repair by enhancing bone formation. In the present study we defined the role of EP1 in bone maintenance and homeostasis during aging and in response to ovariectomy. The femur and L4 vertebrae of wild type (WT) and EP1(-/-) mice were examined at 2-months, 6-months, and 1-year of age, and in WT and EP1(-/-) mice following ovariectomy (OVX) or sham surgery. Bone volume fraction, trabecular architecture and mechanical properties were maintained during aging in EP1(-/-) mice to a greater degree than age-matched WT mice. Moreover, significant increases in bone formation rate (BFR) (+60%) and mineral apposition rate (MAR) (+50%) were observed in EP1(-/-), relative to WT, while no change in osteoclast number and osteoclast surface were observed. Following OVX, loss of EP1 was protective against bone loss in both femur and L4 vertebrae, with increased bone volume/total volume (BV/TV) (+32% in femur) and max load at failure (+10% in femur) relative to WT OVX, likely resulting from the increased bone formation rate that was observed in these mice. Taken together these studies identify inhibition of EP1 as a potential therapeutic approach to suppress bone loss in aged or post-menopausal patients.
authors.affiliation: Center for Musculoskeletal Research, Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY 14642, United States.
authors.forename: Minjie
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Center for Musculoskeletal Research, Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY 14642, United States.
authors.forename: Marina
authors.initials: M
authors.lastname: Feigenson
authors.affiliation: Center for Musculoskeletal Research, Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY 14642, United States.
authors.forename: Tzong-jen
authors.initials: TJ
authors.lastname: Sheu
authors.affiliation: Center for Musculoskeletal Research, Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY 14642, United States; Department of Biomedical Engineering, University of Rochester, Rochester, NY 14627, United States.
authors.forename: Hani A
authors.initials: HA
authors.lastname: Awad
authors.affiliation: Center for Musculoskeletal Research, Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY 14642, United States.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
authors.affiliation: Center for Musculoskeletal Research, Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY 14642, United States.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Jonason
authors.affiliation: Center for Musculoskeletal Research, Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY 14642, United States.
authors.forename: Alayna E
authors.initials: AE
authors.lastname: Loiselle
authors.affiliation: Center for Musculoskeletal Research, Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY 14642, United States; Department of Orthopaedic Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States. Electronic address: okeefer@wudosis.wustl.edu.
authors.forename: Regis J
authors.initials: RJ
authors.lastname: O'Keefe
mesh_terms: D000375:Aging; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002454:Cell Differentiation; D005260:Female; D006706:Homeostasis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010010:Osteoclasts / Q000166:cytology; D010052:Ovariectomy; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013314:Stress, Mechanical; D055114:X-Ray Microtomography
chemical_list: C545636:Ptger1 protein, mouse; D058306:Receptors, Prostaglandin E, EP1 Subtype
keywords: Age-related bone loss; Bone homeostasis; EP1; Mouse model; Ovariectomy; PGE2