RRC ID 51670
Author Nakabayashi H, Aoyama S, Kawahara M, Nagamune T.
Title Differentiation signalobody: Demonstration of antigen-dependent osteoclast differentiation from a progenitor cell line.
Journal J Biosci Bioeng
Abstract A "cytokine-less" in vitro differentiation method would be promising for cost-effective mass production of cells used for regenerative medicine. In this study, we developed a differentiation signalobody S-RANK, in which the extracellular domain of receptor activator of nuclear factor kappa-B (RANK) is replaced with a single-chain variable fragment (scFv) to attain signaling in response to an inexpensive antigen. A murine macrophage cell line RAW264, which is known to differentiate into an osteoclast by RANK ligand (RANKL), was lentivirally transduced with S-RANK. When the resultant cells were cultured with a specific antigen, the cells differentiated into multinucleated tartrate-resistant acid phosphatase-positive osteoclasts. The differentiation efficiency was almost comparable to those induced by RANKL. In addition, the signaling analysis demonstrated that nuclear factor kappa-B and mitogen-activated protein kinase signaling pathways, which are the major signaling pathways downstream of wild-type RANK, were also activated by S-RANK. These results demonstrate that S-RANK sufficiently mimics signal transduction of wild-type RANK. Differentiation signalobodies may be applied for controlling differentiation of other cell types by using appropriate signaling domains.
Volume 122(3)
Pages 357-63
Published 2016-9
DOI 10.1016/j.jbiosc.2016.02.010
PII S1389-1723(16)00047-5
PMID 26979343
MeSH Animals Antigens / immunology Cell Differentiation* / drug effects Cell Line Macrophages / cytology Macrophages / drug effects Mice Mitogen-Activated Protein Kinases / metabolism NF-kappa B / agonists NF-kappa B / metabolism Osteoclasts / cytology* Osteoclasts / drug effects Protein Domains RANK Ligand / pharmacology Receptor Activator of Nuclear Factor-kappa B / chemistry* Receptor Activator of Nuclear Factor-kappa B / pharmacology* Signal Transduction / drug effects Single-Chain Antibodies / chemistry Single-Chain Antibodies / immunology Single-Chain Antibodies / pharmacology* Stem Cells / cytology* Stem Cells / drug effects
IF 2.032
Times Cited 1
Human and Animal Cells RAW 264(RCB0535)