NELL-1 promotes cell adhesion and differentiation via integrinβ1

Jia Shen, Aaron W. James, Jonguk Chung, Kiho Lee, James B. Zhang, Stephanie Ho, Kevin S. Lee, Toyong M. Kim, Tomoaki Niimi, Shun'Ichi Kuroda, Kang Ting, Chia Soo

Research output: Contribution to journalArticlepeer-review

Abstract

NELL-1 (Nel-like molecule-1) is a secreted osteogenic growth factor first identified in human craniosynostosis (CS) patients. NELL-1 protein has been observed to promote bone and cartilage differentiation and to suppress adipogenesis in both in vitro and in vivo models. Despite these findings, the cell surface receptors of NELL-1 have remained unknown. In this study, we observed for the first time that NELL-1 promotes cell adherence in multiple cell lines, including ST2, C3H10T1/2, M2-10B4, ATDC5, and MC3T3 cells. Additionally, we found that NELL-1 binds to extracellular Integrinβ1 and induces cell focal adhesion. By utilizing siRNA methods, we determined that NELL-1 cell surface binding and enhanced cell attachment were dependent on Integrinβ1 expression. Finally, we observed that pre-coating of culture dishes or PLGA (polylactic-co-glycolic acid) scaffold with NELL-1 resulted in a significant increase in both cell attachment and osteogenic differentiation. Our results identify for the first time a cell surface target of NELL-1, Integrinβ1, and elucidate new functions of NELL-1 in promoting cell adherence and osteogenic differentiation.

Original languageEnglish (US)
Pages (from-to)3620-3628
Number of pages9
JournalJournal of cellular biochemistry
Volume113
Issue number12
DOIs
StatePublished - Dec 2012
Externally publishedYes

Keywords

  • CELL ADHERENCE
  • FAK
  • INTEGRINβ1
  • NELL-1
  • OSTEOGENIC DIFFERENTIATION
  • ST2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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