Sodium-Dependent Phosphate Transporters in Osteoclast Differentiation and Function

Albano, Giuseppe; Moor, Matthias; Dolder, Silvia; Siegrist, Mark; Wagner, Carsten A.; Biber, Jürg; Hernando, Nati; Hofstetter, Wilhelm; Bonny, Olivier; Fuster, Daniel Guido (2015). Sodium-Dependent Phosphate Transporters in Osteoclast Differentiation and Function. PLoS ONE, 10(4), e0125104. Public Library of Science 10.1371/journal.pone.0125104

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Albano, Giuseppe; Dolder, Silvia; Siegrist, Mark; Hofstetter, Wilhelm and Fuster, Daniel Guido

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Daniel Guido Fuster

Date Deposited:

04 Jun 2015 13:19

Last Modified:

07 Nov 2016 08:56

Publisher DOI:

10.1371/journal.pone.0125104

PubMed ID:

25910236

BORIS DOI:

10.7892/boris.69224

URI:

https://boris.unibe.ch/id/eprint/69224

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