NELL-1 binds to APR3 affecting human osteoblast proliferation and differentiation

FEBS Lett. 2011 Aug 4;585(15):2410-8. doi: 10.1016/j.febslet.2011.06.024. Epub 2011 Jun 26.


Nel-like protein 1 (NELL-1) is an osteoinductive molecule associated with premature calvarial suture closure. Here we identified apoptosis related protein 3 (APR3), a membrane protein known as a proliferation suppressor, as a binding protein of NELL-1 by biopanning. NELL-1 and APR3 colocalized on the nuclear envelope of human osteoblasts. NELL-1 significantly inhibited proliferation of osteoblasts co-transfected with APR3 through further down-regulation of Cyclin D1. The co-expression of NELL-1 and APR3 enhanced Ocn and Bsp expression and mineralization. RNAi of APR3 significantly reduced the differentiation effect of NELL-1. These findings suggest that the effects of NELL-1 on osteoblastic differentiation and proliferation are partly through binding to APR3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism*
  • Cell Differentiation*
  • Cell Proliferation*
  • Cells, Cultured
  • Cyclin D1 / metabolism
  • Humans
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / physiology
  • Osteoblasts / cytology*
  • Osteoblasts / metabolism*
  • Peptide Library
  • Protein Binding / physiology


  • Apoptosis Regulatory Proteins
  • NELL1 protein, human
  • Nerve Tissue Proteins
  • Peptide Library
  • apoptosis related protein 3, human
  • Cyclin D1