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Effect of lysophosphatidic acid receptor inhibition on bone changes in ovariectomized mice

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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.

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Acknowledgments

We thank Dra. M. Jesus Ramirez from Dpto. de Ciencias de la Salud (Universidad de Jaen) and Dra. L.M. Seoane and L. Senin from Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS) for advice with ovariectomy. This work was supported by grant PI11/02197, by RETICS Program, RD08/0075 (RIER), all from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III with participation of FEDER funds (European Union).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 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

    Beatriz Orosa, Paula Martínez, Antonio González, Juan J. Gómez-Reino & Carmen Conde

  2. Trabeculae S.L., Technological Park of Galicia, 32900, Ourense, Spain

    David Guede

  3. Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain

    David Guede & José R. Caeiro

  4. Servicio de Cirugía Ortopédica y Traumatología, Hospital Clínico Universitario de Santiago de Compostela (CHUS), SERGAS, Travesía da Choupana s/n, Santiago de Compostela, 15706, Spain

    José R. Caeiro

  5. Departamento de Medicina, Universidade de Santiago de Compostela, San Francisco s/n, 15782, Santiago de Compostela, Spain

    Juan J. Gómez-Reino

Authors
  1. Beatriz Orosa
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  2. Paula Martínez
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  3. Antonio González
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  4. David Guede
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  5. José R. Caeiro
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  6. Juan J. Gómez-Reino
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  7. Carmen Conde
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Correspondence to Carmen Conde.

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Orosa, B., Martínez, P., González, A. et al. Effect of lysophosphatidic acid receptor inhibition on bone changes in ovariectomized mice. J Bone Miner Metab 33, 383–391 (2015). https://doi.org/10.1007/s00774-014-0607-5

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  • DOI: https://doi.org/10.1007/s00774-014-0607-5

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