Sodium-dependent Phosphate Transporters in Osteoclast Differentiation and Function

PLoS One. 2015 Apr 24;10(4):e0125104. doi: 10.1371/journal.pone.0125104. eCollection 2015.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Resorption / metabolism
  • Bone Resorption / physiopathology
  • Cell Differentiation / physiology*
  • Cell Line
  • Ion Transport / physiology
  • Mice
  • Osteoclasts / metabolism*
  • Osteoclasts / physiology*
  • Phosphates / metabolism*
  • RANK Ligand
  • Sodium / metabolism*
  • Sodium-Phosphate Cotransporter Proteins, Type II / metabolism*
  • Sodium-Phosphate Cotransporter Proteins, Type III / metabolism*


  • Phosphates
  • RANK Ligand
  • Sodium-Phosphate Cotransporter Proteins, Type II
  • Sodium-Phosphate Cotransporter Proteins, Type III
  • Sodium

Grant support

Swiss National Science Foundation NCCR Trancure to DF, WH. Swiss National Science Foundation NCCR Kidney.CH to DF, JB, CW, NH, OB. Swiss National Science Foundation grants # 3100A0_135503 and 3100A0_152829 to DF. Prof. Max Cloetta Foundation grant to DF. Swiss National Science Foundation grant # PP00P3-133648 to OB.