title: Identification of acid-sensing ion channels in bone.
abstract: Bone balances serum pH variations and both osteoclasts and osteoblasts are regulated by subtle changes in pH. The aim of the current study was to identify molecules in bone that can sense pH. Interesting candidates are the acid-sensing ion channels (ASICs). In bone, ASIC2 and ASIC3 were most abundant, while in chondrocytes it was ASIC1. Isolated human monocytes expressed ASIC1, -2, and -3, which persisted after induction to osteoclast differentiation, albeit to a lower level. In human osteoblasts ASIC1, ASIC2, and ASIC3 mRNAs were shown. Western blot and immunostaining confirmed this at protein level. ASIC4 expression was always very low abundant. For the first time, we demonstrated ASICs in human skeleton, providing a means to sense and respond to differences in extracellular pH.
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands.
authors.forename: Holger
authors.initials: H
authors.lastname: Jahr
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Driel
authors.forename: Gerjo J V M
authors.initials: GJ
authors.lastname: van Osch
authors.forename: Harrie
authors.initials: H
authors.lastname: Weinans
authors.forename: Johannes P T M
authors.initials: JP
authors.lastname: van Leeuwen
mesh_terms: D062565:Acid Sensing Ion Channels; D001842:Bone and Bones / Q000378:metabolism*; D002113:Calcification, Physiologic; D002478:Cells, Cultured; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism; D053495:Osteopontin; D012333:RNA, Messenger / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D015222:Sodium Channels / Q000032:analysis / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism
chemical_list: C568266:ASIC1 protein, human; C568270:ASIC4 protein, human; D062565:Acid Sensing Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D015222:Sodium Channels; D053495:Osteopontin