Absence of the lysophosphatidic acid receptor LPA1 results in abnormal bone development and decreased bone mass
| Autor: | Laurence Vico, Isabelle Gennero, Danielle Laurencin, Jerold Chun, Jackie Rue, Nicole Malet, Gérard Brunel, Marianne Mus, Fabienne Briand-Mésange, Philippe Bourin, Sara Laurencin-Dalicieux, Nicolas Beton, Françoise Conte-Auriol, Akira Tokumura, Jean Pierre Salles, Richard O.C. Oreffo |
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| Přispěvatelé: | Laboratoire de Biochimie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Faculté de Chirurgie Dentaire, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Endocrine and Bone Diseases Unit, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Department of Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, Laboratoire de thérapie cellulaire (EFS), Etablissement Français du Sang, Université de Lyon, Contraintes mécaniques et tissu osseux, Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bone and Joint Research Group, University of Southampton Medical School, Department of Molecular Biology Helen L. Dorris, The Scripps Research Institute |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Bone density
Physiology Endocrinology Diabetes and Metabolism Osteoporosis Osteoclasts Mice chemistry.chemical_compound 0302 clinical medicine Bone Density Osteogenesis Bone cell Lysophosphatidic acid Protein Isoforms Receptors Lysophosphatidic Acid Mesenchymal stem cell Mice Knockout 0303 health sciences Osteoblast [SDV.BA]Life Sciences [q-bio]/Animal biology Cell Differentiation Cell biology medicine.anatomical_structure 030220 oncology & carcinogenesis lipids (amino acids peptides and proteins) medicine.medical_specialty Histology Nutritional Status Bone Marrow Cells Biology Article Bone and Bones 03 medical and health sciences Paracrine signalling Internal medicine medicine Animals Bone 030304 developmental biology Osteoblasts LPA1 Mesenchymal Stem Cells X-Ray Microtomography medicine.disease Mice Inbred C57BL Endocrinology chemistry Cortical bone Bone marrow Lysophospholipids Biomarkers |
| Zdroj: | BONE BONE, Elsevier, 2011, 49, pp.395-403. ⟨10.1016/j.bone.2011.04.018⟩ |
| ISSN: | 8756-3282 |
| Popis: | International audience; Lysophosphatidic acid (LPA) is a lipid mediator that acts in paracrine systems via interaction with a subset of G protein-coupled receptors (GPCRs). LPA promotes cell growth and differentiation, and has been shown to be implicated in a variety of developmental and pathophysiological processes. At least 6 LPA GPCRs have been identified to date: LPA1-LPA6. Several studies have suggested that local production of LPA by tissues and cells contributes to paracrine regulation, and a complex interplay between LPA and its receptors, LPA1 and LPA4,is believed to be involved in the regulation of bone cell activity. In particular, LPA1may activate both osteoblasts and osteoclasts. However, its role has not as yet been examined with regard to the overall status of bone in vivo. We attempted to clarify this role by defining the bone phenotype of LPA1 (−/−) mice. These mice demonstrated significant bone defects and low bone mass, indicating that LPA1 plays an important role in osteogenesis. The LPA1(−/−) mice also presented growth and sternal and costal abnormalities, which highlights the specific roles of LPA1 during bone development. Microcomputed tomography and histological analysis demonstrated osteoporosis in the trabecular and cortical bone of LPA1 (−/−) mice. Finally, bone marrow mesenchymal progenitors from these mice displayed decreased osteoblastic differentiation. These results suggest that LPA1 strongly influences bone development both qualitatively and quantitatively and that, in vivo, its absence results in decreased osteogenesis with no clear modification of osteoclasis. They open perspectives for a better understanding of the role of the LPA/LPA1 paracrine pathway in bone pathophysiology. |
| Databáze: | OpenAIRE |
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