Details

Autor(en) / Beteiligte

• Salles, Jean Pierre
• Laurencin-Dalicieux, Sara
• Conte-Auriol, Françoise
• Briand-Mésange, Fabienne
• Gennero, Isabelle

Titel

Bone defects in LPA receptor genetically modified mice

Ist Teil von

• Biochimica et biophysica acta, 2013-01, Vol.1831 (1), p.93-98

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• LPA and LPA1 have been shown to increase osteoblastic proliferation and differentiation as well as activation of osteoclasts. Cell and animal model studies have suggested that LPA is produced by bone cells and bone tissues. We obtained data from invalidated mice which support the hypothesis that LPA1 is involved in bone development by promoting osteogenesis. LPA1-invalidated mice demonstrate growth and sternal and costal abnormalities, which highlights the specific roles of LPA1 during bone development. Microcomputed tomography and histological analysis demonstrate osteoporosis in the trabecular and cortical bone of LPA1-invalidated mice. Moreover, bone marrow mesenchymal progenitors from these mice displayed decreased osteoblastic differentiation. Infrared analysis did not indicate osteomalacia in the bone tissue of LPA1-invalidated mice. LPA1 displays opposite effects to LPA4 on the related G proteins Gi and Gs, responsible for decrease and increase of the cAMP level respectively, which itself is essential to the control of osteoblastic differentiation. The opposite effects of LPA1 and LPA4 during osteoblastic differentiation support the possibility that new pharmacological agents derived from the LPA pathways could be found and used in clinical practice to positively influence bone formation and treat osteoporosis. The paracrine effect of LPA is potentially modulated by its concentration in bone tissues, which may result from various intracellular and extracellular pathways. The relevance of LPA1 in bone remodeling, as a receptor able to influence both osteoblast and osteoclast activity, still deserves further clarification. This article is part of a Special Issue entitled Advances in Lysophospholipid Research. ► Lysophosphatidic acid is present in bone tissues, produced by different pathways and cells. ► LPA1 receptor is involved in bone cells proliferation and differentiation. ► LPA1-invalidated mice display bone abnormalities. ► Microcomputed tomography and histological analysis demonstrate osteoporosis in LPA1-invalidated mice. ► Stem cells from LPA1-invalidated mice demonstrate decreased potentiality for differentiation and mineralization.