Bone defects in LPA receptor genetically modified mice

作者：Salles Jean Pierre^*; Laurencin Dalicieux Sara; Conte Auriol Francoise; Briand Mesange Fabienne; Gennero Isabelle

来源：Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, 2013, 1831(1): 93-98.

DOI：10.1016/j.bbalip.2012.07.018

• LPA1
• Lysophosphatidic acid
• Parathyroid hormone-related peptide
• Bone resorption
• Osteogenesis
• Osteoporosis

LPA and LPA(1) 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 LPA(1) is involved in bone development by promoting osteogenesis. LPA(1)-invalidated mice demonstrate growth and sternal and costal abnormalities, which highlights the specific roles of LPA(1) during bone development. Microcomputed tomography and histological analysis demonstrate osteoporosis in the trabecular and cortical bone of LPA(1)-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 LPA(1)-invalidated mice. LPA(1) displays opposite effects to LPA(4) on the related G proteins G(i) and G(s), responsible for decrease and increase of the cAMP level respectively, which itself is essential to the control of osteoblastic differentiation. The opposite effects of LPA(1) and LPA(4) 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 LPA(1) 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.

• 出版日期2013-1