Absence of the lysophosphatidic acid receptor LPA1 results in abnormal bone development and decreased bone mass

• Published in: Bone (New York, N.Y.) N.Y.), 2011-09, Vol.49 (3), p.395-403
• Main Authors: Gennero, Isabelle, Laurencin-Dalicieux, Sara, Conte-Auriol, Françoise, Briand-Mésange, Fabienne, Laurencin, Danielle, Rue, Jackie, Beton, Nicolas, Malet, Nicole, Mus, Marianne, Tokumura, Akira, Bourin, Philippe, Vico, Laurence, Brunel, Gérard, Oreffo, Richard O.C, Chun, Jerold, Salles, Jean Pierre
• Format: Article
• Language: English
• Subjects: Animal biology; Animals; Biological and medical sciences; Biomarkers - metabolism; Bone and Bones - abnormalities; Bone and Bones - anatomy & histology; Bone and Bones - diagnostic imaging; Bone and Bones - physiology; Bone Density; Bone Marrow Cells - cytology; Bone Marrow Cells - physiology; Cell Differentiation - physiology; Cell physiology; Fundamental and applied biological sciences. Psychology; Life Sciences; Lysophospholipids - metabolism; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mineralization, calcification; Molecular and cellular biology; Nutritional Status; Orthopedics; Osteoblasts - cytology; Osteoblasts - physiology; Osteoclasts - cytology; Osteoclasts - physiology; Osteogenesis - physiology; Protein Isoforms - genetics; Protein Isoforms - metabolism; Receptors, Lysophosphatidic Acid - genetics; Receptors, Lysophosphatidic Acid - metabolism; Skeleton and joints; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: osteoarticular system, musculoskeletal system; X-Ray Microtomography
• ISSN: 8756-3282; 1873-2763; 8756-3282
• DOI: 10.1016/j.bone.2011.04.018

Abstract 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, LPA1 may 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.