NELL-1 promotes cell adhesion and differentiation via Integrinβ1

Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California 90095.
Journal of Cellular Biochemistry (Impact Factor: 3.26). 12/2012; 113(12):3620-8. DOI: 10.1002/jcb.24253
Source: PubMed

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. J. Cell. Biochem. 113: 3620-3628, 2012. © 2012 Wiley Periodicals, Inc.

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    • "Integrinβ1 was recently identified as the first cell surface receptor of NELL-1 [159]. Cell surface binding in a pre-osteoblast cell line required Integrinβ1 expression [159]. Moreover, siRNA for Integrinβ1 blocked at least some of the cellular effects of NELL-1, including induction of pre-osteoblast attachment [159]. "
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