NELL-1 increases pre-osteoblast mineralization using both phosphate transporter Pit1 and Pit2

Catherine M. Cowan, Xinli Zhang, Aaron W. James, T. Mari Kim, Nichole Sun, Benjamin Wu, Kang Ting, Chia Soo

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


NELL-1 is a potent osteoinductive molecule that enhances bone formation in multiple animal models through currently unidentified pathways. In the present manuscript, we hypothesized that NELL-1 may regulate osteogenic differentiation accompanied by alteration of inorganic phosphate (Pi) entry into the osteoblast via sodium dependent phosphate (NaPi) transporters. To determine this, MC3T3-E1 pre-osteoblasts were cultured in the presence of recombinant human (rh)NELL-1 or rhBMP-2. Analysis was performed for intracellular Pi levels through malachite green staining, Pit-1 and Pit-2 expression, and forced upregulation of Pit-1 and Pit-2. Results showed rhNELL-1 to increase MC3T3-E1 matrix mineralization and Pi influx associated with activation of both Pit-1 and Pit-2 channels, with significantly increased Pit-2 production. In contrast, Pi transport elicited by rhBMP-2 showed to be associated with increased Pit-1 production only. Next, neutralizing antibodies against Pit-1 and Pit-2 completely abrogated the Pi influx effect of rhNELL-1, suggesting rhNELL-1 is dependent on both transporters. These results identify one potential mechanism of action for rhNELL-1 induced osteogenesis and highlight a fundamental difference between NELL-1 and BMP-2 signaling.

Original languageEnglish (US)
Pages (from-to)351-357
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - Jun 8 2012
Externally publishedYes


  • BMP-2
  • MC3T3-E1
  • NELL-1
  • Osteogenesis
  • Phosphate transport
  • Pit

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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