title: Lysophosphatidic acid and calcitriol co-operate to promote human osteoblastogenesis: requirement of albumin-bound LPA.
abstract: Lysophosphatidic acid (LPA), a pleiotropic signalling lipid is assuming growing significance in osteoblast biology. Although committed osteoblasts from several mammalian species are receptive to LPA far less is known about the potential for LPA to influence osteoblast formation from their mesenchymal progenitors. An essential factor for both bone development and post-natal bone growth and homeostasis is the active metabolite of vitamin D3, calcitriol (D3). Previously we reported how a combination of LPA and D3 synergistically co-operated to enhance the differentiation of immature human osteoblasts. Herein we provide evidence for the formation of human osteoblasts from multiple, primary human bone marrow derived stromal (stem) cells (hBMSCs). Importantly osteoblast development from hBMSCs only occurred when LPA was administered as a complex with albumin, its natural carrier. Collectively our findings support a co-operative role of LPA and D3 in osteoblastogenesis, findings which may aid the development of novel treatment strategies for bone repair.
authors.affiliation: Musculoskeletal Research Unit, Avon Orthopaedic Centre, Southmead Hospital, Bristol, United Kingdom. j.p.mansell@bris.ac.uk
authors.forename: J P
authors.initials: JP
authors.lastname: Mansell
authors.forename: M
authors.initials: M
authors.lastname: Nowghani
authors.forename: M
authors.initials: M
authors.lastname: Pabbruwe
authors.forename: I C
authors.initials: IC
authors.lastname: Paterson
authors.forename: A J
authors.initials: AJ
authors.lastname: Smith
authors.forename: A W
authors.initials: AW
authors.lastname: Blom
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects*; D000368:Aged; D000469:Alkaline Phosphatase / Q000737:chemistry / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D001861:Bone Regeneration / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology; D004337:Drug Carriers; D057075:Enzyme Assays; D005260:Female; D015870:Gene Expression; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology*; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism; D012709:Serum Albumin
chemical_list: D004337:Drug Carriers; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D012709:Serum Albumin; D002762:Cholecalciferol; D000469:Alkaline Phosphatase; D002117:Calcitriol; C032881:lysophosphatidic acid