NELL-1 promotes cell adhesion and differentiation via Integrinβ1.
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.
Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jia
J
Shen
Aaron W
AW
James
Jonguk
J
Chung
Kiho
K
Lee
James B
JB
Zhang
Stephanie
S
Ho
Kevin S
KS
Lee
Toyong M
TM
Kim
Tomoaki
T
Niimi
Shun'ichi
S
Kuroda
Kang
K
Ting
Chia
C
Soo
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D022001:Focal Adhesions; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010012:Osteogenesis; D011100:Polyglycolic Acid / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011485:Protein Binding; D025941:Protein Interaction Mapping; D034741:RNA, Small Interfering; D016415:Sequence Alignment
D002135:Calcium-Binding Proteins; D019012:Integrin beta1; C104144:NELL1 protein, human; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid