RRC ID 60131
Author Sone E, Noshiro D, Ikebuchi Y, Nakagawa M, Khan M, Tamura Y, Ikeda M, Oki M, Murali R, Fujimori T, Yoda T, Honma M, Suzuki H, Ando T, Aoki K.
Title The induction of RANKL molecule clustering could stimulate early osteoblast differentiation.
Journal Biochem Biophys Res Commun
Abstract We recently found that the membrane-bound receptor activator of NF-κB ligand (RANKL) on osteoblasts works as a receptor to stimulate osteoblast differentiation, however, the reason why the RANKL-binding molecules stimulate osteoblast differentiation has not been well clarified. Since the induction of cell-surface receptor clustering is known to lead to cell activation, we hypothesized that the induction of membrane-RANKL clustering on osteoblasts might stimulate osteoblast differentiation. Immunoblotting showed that the amount of RANKL on the membrane was increased by the RANKL-binding peptide OP3-4, but not by osteoprotegerin (OPG), the other RANKL-binding molecule, in Gfp-Rankl-transfected ST2 cells. Observation under a high-speed atomic force microscope (HS-AFM) revealed that RANKL molecules have the ability to form clusters. The induction of membrane-RANKL-OPG-Fc complex clustering by the addition of IgM in Gfp-Rankl-transfected ST2 cells could enhance the expression of early markers of osteoblast differentiation to the same extent as OP3-4, while OPG-Fc alone could not. These results suggest that the clustering-formation of membrane-RANKL on osteoblasts could stimulate early osteoblast differentiation.
Volume 509(2)
Pages 435-440
Published 2019-2-5
DOI 10.1016/j.bbrc.2018.12.093
PII S0006-291X(18)32742-6
PMID 30594398
MeSH Animals Binding Sites Cell Differentiation / drug effects* Cell Line Cell Membrane / drug effects Cell Membrane / metabolism Cell Membrane / ultrastructure Gene Expression Regulation Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Immunoglobulin Fc Fragments / genetics Immunoglobulin Fc Fragments / metabolism Immunoglobulin M / genetics Immunoglobulin M / metabolism Mice Microscopy, Atomic Force Models, Molecular Oligopeptides / chemistry Oligopeptides / metabolism Oligopeptides / pharmacology* Osteoblasts / drug effects* Osteoblasts / metabolism Osteoblasts / ultrastructure Osteoprotegerin / genetics Osteoprotegerin / metabolism Peptidomimetics / chemistry Peptidomimetics / metabolism Peptidomimetics / pharmacology* Protein Binding RANK Ligand / genetics* RANK Ligand / metabolism Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Signal Transduction Time Factors
IF 2.705
Times Cited 3
Human and Animal Cells ST2(RCB0224)