title: Effect of lysophosphatidic acid receptor inhibition on bone changes in ovariectomized mice.
abstract: Pharmacological inhibition of signaling through lysophosphatidic acid (LPA) receptors reduces bone erosions in an experimental model of arthritis by mechanisms involving reduced osteoclast differentiation and bone resorption and increased differentiation of osteoblasts and bone mineralization. These results led us to hypothesize that LPA receptor inhibition would be beneficial in osteoporosis. Our aim was to test this hypothesis with the LPA receptor antagonist, Ki16425, in ovariectomized mice, a model of postmenopausal osteoporosis. Ovariectomized mice treated with Ki16425 showed bone loss similar to that observed in the controls. Osteoblast markers, Alpl, Bglap and Col1a1, were increased at the mRNA level but no changes were detected in serum. No additional difference was observed in the Ki16425-treated mice relative to the ovariectomized controls with regard to osteoclast function markers or assays of matrix mineralization or osteoclast differentiation. Thus, pharmacological inhibition of LPA receptor was not beneficial for preventing bone loss in ovariectomized mice, indicating that its favorable effect on bone remodeling is less general than hypothesized.
authors.affiliation: Laboratorio de Investigación 8 y Servicio de Reumatología, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago de Compostela (CHUS), SERGAS, Travesía da Choupana s/n, Santiago de Compostela, 15706, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Orosa
authors.forename: Paula
authors.initials: P
authors.lastname: Martínez
authors.forename: Antonio
authors.initials: A
authors.lastname: González
authors.forename: David
authors.initials: D
authors.lastname: Guede
authors.forename: José R
authors.initials: JR
authors.lastname: Caeiro
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gómez-Reino
authors.forename: Carmen
authors.initials: C
authors.lastname: Conde
mesh_terms: D000818:Animals; D016723:Bone Remodeling; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007555:Isoxazoles / Q000737:chemistry; D008246:Lysophospholipids / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology; D010024:Osteoporosis / Q000378:metabolism; D015663:Osteoporosis, Postmenopausal / Q000378:metabolism; D010052:Ovariectomy; D011422:Propionates / Q000737:chemistry; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D055114:X-Ray Microtomography
chemical_list: C477898:3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid; D007555:Isoxazoles; D008246:Lysophospholipids; D011422:Propionates; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid