title: P2X7Rs are involved in cell death, growth and cellular signaling in primary human osteoblasts.
abstract: The ionotropic ATP-gated P2X7 receptor (P2X7R) is involved in the regulation of many physiological functions including bone metabolism. Several studies on osteoblasts from rodents and human osteoblast-like cell lines have addressed the expression and function of P2X7R on these bone-forming cells however; its role in human primary osteoblasts has not yet been reported. The aim of this study was to assess the expression of the P2X7R in bone marrow-derived stromal cells and in primary human trabecular osteoblasts and to determine the function in bone formation and cell signaling. We report that osteoblasts derived from human trabecular explants express a functional P2X7R capable of agonist-induced increase in intracellular calcium concentration and a positive permeability to fluorescent dyes. These osteoblasts are fully differentiated cells with alkaline phosphatase activity and the ability to form mineralized nodules. We show that the transcriptional regulation of osteoblastic markers can be modulated by P2X7R activity or blockade thereby influencing the differentiation, proliferation and bone matrix formation by these primary human osteoblasts. Finally, we demonstrate that the P2X7R is involved in propagation of mechanically-induced intercellular signaling in addition to the known mechanisms involving calcium signaling via P2Y2 receptors and gap junction.
authors.affiliation: Research Centre for Ageing and Osteoporosis, Department of Clinical Biochemistry, Rigshospitalet, Denmark.
authors.forename: Ankita
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Research Centre for Ageing and Osteoporosis, Department of Clinical Biochemistry, Rigshospitalet, Denmark.
authors.forename: Zanne
authors.initials: Z
authors.lastname: Henriksen
authors.affiliation: Research Centre for Ageing and Osteoporosis, Department of Clinical Biochemistry, Rigshospitalet, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Syberg
authors.affiliation: Research Centre for Ageing and Osteoporosis, Department of Clinical Biochemistry, Rigshospitalet, Denmark.
authors.forename: Solveig
authors.initials: S
authors.lastname: Petersen
authors.affiliation: Research Centre for Ageing and Osteoporosis, Department of Clinical Biochemistry, Rigshospitalet, Denmark.
authors.forename: Derya
authors.initials: D
authors.lastname: Aslan
authors.affiliation: Research Centre for Ageing and Osteoporosis, Department of Clinical Biochemistry, Rigshospitalet, Denmark.
authors.forename: Marie
authors.initials: M
authors.lastname: Solgaard
authors.affiliation: Department of Orthopedic Surgery, Kolding Hospital, Kolding, Denmark.
authors.forename: Nis
authors.initials: N
authors.lastname: Nissen
authors.affiliation: Department of Orthopedic Surgery, Copenhagen University Hospital Hvidovre, Denmark.
authors.forename: Tommy Korsgaard
authors.initials: TK
authors.lastname: Larsen
authors.affiliation: Research Centre for Ageing and Osteoporosis, Department of Endocrinology, Rigshospitalet, Denmark; Faculty of Health Sciences, Copenhagen University, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Schwarz
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Steinberg
authors.affiliation: Research Centre for Ageing and Osteoporosis, Department of Clinical Biochemistry, Rigshospitalet, Denmark; OPEN, Odense Patient data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: niklas@dadlnet.dk.
authors.forename: Niklas Rye
authors.initials: NR
authors.lastname: Jørgensen
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002113:Calcification, Physiologic; D020013:Calcium Signaling; D000071556:Cancellous Bone / Q000166:cytology; D016923:Cell Death; D049109:Cell Proliferation; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D058486:Receptors, Purinergic P2X7; D000469:Alkaline Phosphatase
keywords: Calcium signaling; Osteoblast; P2X7R