title: Sodium-dependent phosphate transporters in osteoclast differentiation and function.
abstract: Osteoclasts are multinucleated bone degrading cells. Phosphate is an important constituent of mineralized bone and released in significant quantities during bone resorption. Molecular contributors to phosphate transport during the resorptive activity of osteoclasts have been controversially discussed. This study aimed at deciphering the role of sodium-dependent phosphate transporters during osteoclast differentiation and bone resorption. Our studies reveal RANKL-induced differential expression of sodium-dependent phosphate transport protein IIa (NaPi-IIa) transcript and protein during osteoclast development, but no expression of the closely related NaPi-IIb and NaPi-IIc SLC34 family isoforms. In vitro studies employing NaPi-IIa-deficient osteoclast precursors and mature osteoclasts reveal that NaPi-IIa is dispensable for bone resorption and osteoclast differentiation. These results are supported by the analysis of structural bone parameters by high-resolution microcomputed tomography that yielded no differences between adult NaPi-IIa WT and KO mice. By contrast, both type III sodium-dependent phosphate transporters Pit-1 and Pit-2 were abundantly expressed throughout osteoclast differentiation, indicating that they are the relevant sodium-dependent phosphate transporters in osteoclasts and osteoclast precursors. We conclude that phosphate transporters of the SLC34 family have no role in osteoclast differentiation and function and propose that Pit-dependent phosphate transport could be pivotal for bone resorption and should be addressed in further studies.
authors.affiliation: Division of Nephrology, Hypertension and Clinical Pharmacology, University Hospital of Bern, Bern, Switzerland; Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland; NCCR Transcure, University of Bern, Bern, Switzerland; NCCR Kidney.CH, University of Zürich, Zürich, Switzerland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Albano
authors.affiliation: Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland; NCCR Kidney.CH, University of Zürich, Zürich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Moor
authors.affiliation: NCCR Transcure, University of Bern, Bern, Switzerland; Group for Bone Biology and Orthopaedic Research, Department of Clinical Research, University of Bern, Bern, Switzerland; NCCR Kidney.CH, University of Zürich, Zürich, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dolder
authors.affiliation: NCCR Transcure, University of Bern, Bern, Switzerland; Group for Bone Biology and Orthopaedic Research, Department of Clinical Research, University of Bern, Bern, Switzerland; NCCR Kidney.CH, University of Zürich, Zürich, Switzerland.
authors.forename: Mark
authors.initials: M
authors.lastname: Siegrist
authors.affiliation: Institute of Physiology, University of Zürich, Zürich, Switzerland; NCCR Kidney.CH, University of Zürich, Zürich, Switzerland.
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Wagner
authors.affiliation: Institute of Physiology, University of Zürich, Zürich, Switzerland; NCCR Kidney.CH, University of Zürich, Zürich, Switzerland.
authors.forename: Jürg
authors.initials: J
authors.lastname: Biber
authors.affiliation: Institute of Physiology, University of Zürich, Zürich, Switzerland; NCCR Kidney.CH, University of Zürich, Zürich, Switzerland.
authors.forename: Nati
authors.initials: N
authors.lastname: Hernando
authors.affiliation: NCCR Transcure, University of Bern, Bern, Switzerland; Group for Bone Biology and Orthopaedic Research, Department of Clinical Research, University of Bern, Bern, Switzerland; NCCR Kidney.CH, University of Zürich, Zürich, Switzerland.
authors.forename: Willy
authors.initials: W
authors.lastname: Hofstetter
authors.affiliation: Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland; NCCR Kidney.CH, University of Zürich, Zürich, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bonny
authors.affiliation: Division of Nephrology, Hypertension and Clinical Pharmacology, University Hospital of Bern, Bern, Switzerland; Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland; NCCR Transcure, University of Bern, Bern, Switzerland; NCCR Kidney.CH, University of Zürich, Zürich, Switzerland.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Fuster
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism / Q000503:physiopathology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D017136:Ion Transport / Q000502:physiology; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism* / Q000502:physiology*; D010710:Phosphates / Q000378:metabolism*; D053245:RANK Ligand; D012964:Sodium / Q000378:metabolism*; D050610:Sodium-Phosphate Cotransporter Proteins, Type II / Q000378:metabolism*; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000378:metabolism*
chemical_list: D010710:Phosphates; D053245:RANK Ligand; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D012964:Sodium