Expression of the type 1 lysophosphatidic acid receptor in osteoblastic cell lineage controls both bone mineralization and osteocyte specification
| العنوان: | Expression of the type 1 lysophosphatidic acid receptor in osteoblastic cell lineage controls both bone mineralization and osteocyte specification |
|---|---|
| المؤلفون: | Irma Machuca-Gayet, Hélène Follet, Jean-Pierre Salles, Jerold Chun, Isabelle Gennero, Sara Laurencin-Dalacieux, Daniel Bouvard, François Duboeuf, Amri Saber, Richard Rivera, Nicolas Beton, Candide A. Alioli, Delphine Farlay, Léa Demesmay, Olivier Peyruchaud |
| المساهمون: | Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), 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), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Sanford Burnham Prebys Medical Discovery Institute, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), This work was supported by grants from the Institut National de la Santé Et de la Recherche Médicale, the Université Claude Bernard Lyon 1, the Agence Nationale de la Recherche (Grant LYSBONE No. ANR-15-CE14-0010), the Région d’Occitanie (grant Rbio N°15065647), Ipsen Pharma France, Lilly France and Pfizer France., ANR-15-CE14-0010,LYSBONE,Acide lysophosphatidique et contrôle de la masse osseuse(2015), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Peyruchaud, Olivier, Acide lysophosphatidique et contrôle de la masse osseuse - - LYSBONE2015 - ANR-15-CE14-0010 - AAPG2015 - VALID |
| المصدر: | Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, Elsevier, 2020, 1865 (8), pp.158715. ⟨10.1016/j.bbalip.2020.158715⟩ Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, 2020, 1865 (8), pp.158715. ⟨10.1016/j.bbalip.2020.158715⟩ |
| بيانات النشر: | HAL CCSD, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Lpar1, Cellular differentiation, 030209 endocrinology & metabolism, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Osteocytes, Bone remodeling, Mice, 03 medical and health sciences, 0302 clinical medicine, Bone Density, Osteogenesis, Bone cell, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Animals, Receptors, Lysophosphatidic Acid, Bone, Molecular Biology, Mice, Knockout, Bone growth, Mice, Inbred BALB C, LPA(1), Osteoblasts, LPAR1, [SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT], Chemistry, Osteoblast, Osteocyte, Cell Biology, DMP1, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Knockout mice |
| الوصف: | International audience; Lysphosphatidic acid (LPA) is a major natural bioactive lipid mediator whose biological functions affect multiple organs. These include bone as demonstrated by global Lpar1-knockout mice (Lpar1-/-) which present a bone growth defect. LPA acts on all bone cells including osteoblasts, that are responsible for bone formation, and osteoclasts, which are specialized cells that resorb bone. LPA appears as a potential new coupling molecule during bone remodeling. LPA1 is the most ubiquitous LPA receptor among the six LPA receptor family members (LPA1-6). To better understand the specific role of LPA via its receptor LPA1 in osteoblastic cell lineage we generated osteoblast-specific Lpar1 knockout mice (Lpar1-∆Ob) by crossing Lpar1flox/flox and Osx:Cre+ mouse lines. Lpar1-∆Ob mice do not recapitulate the bone defects of Lpar1-/- mice but revealed reduced bone mineralization and decreased cortical thickness, as well as increased bone porosity associated with an augmentation in the lacunae areas of osteocyte and their apoptotic yield. In vitro, primary Lpar1-∆Ob and immortalized cl1-Ob-Lpar1-/- osteoblasts revealed a remarkable premature expression of alkaline phosphatase, reduced cell proliferation associated with decreased YAP-P nuclear accumulation, and reduced mineralization activity. Osteocyte specification is markedly impaired as demonstrated by reduced expression of early (E11) and late (DMP1, DKK1, SOST) osteocyte markers ex vivo in enriched osteocytic fractions of Lpar1-∆Ob mouse bone explants. In addition, E11 expression and dendrite formation induced by FGF2 are markedly impaired in both primary Lpar1-∆Ob and immortalized cl1-Ob-Lpar1-/- osteoblasts. Taken together these results suggest a new role for LPA in bone mass control via bone mineralization and osteocyte function. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1388-1981 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::83f742ffe442cfe3f193d466e5eb10c2Test https://www.hal.inserm.fr/inserm-02611712/documentTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....83f742ffe442cfe3f193d466e5eb10c2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13881981 |
|---|