RRC ID 45072
Author Yamasaki T, Ariyoshi W, Okinaga T, Adachi Y, Hosokawa R, Mochizuki S, Sakurai K, Nishihara T.
Title The dectin 1 agonist curdlan regulates osteoclastogenesis by inhibiting nuclear factor of activated T cells cytoplasmic 1 (NFATc1) through Syk kinase.
Journal J Biol Chem
Abstract Several immune system cell surface receptors are reported to be associated with osteoclastogenesis. Dectin 1, a lectin receptor for β-glucan, is found predominantly on cells of the myeloid lineage. In this study, we examined the effect of the dectin 1 agonist curdlan on osteoclastogenesis. In mouse bone marrow cells and dectin 1-overexpressing RAW 264.7 cells (d-RAWs), curdlan suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation, bone resorption, and actin ring formation in a dose-dependent manner. This was achieved within non-growth inhibitory concentrations at the early stage. Conversely, curdlan had no effect on macrophage colony-stimulating factor-induced differentiation. Furthermore, curdlan inhibited RANKL-induced nuclear factor of activated T cell cytoplasmic 1 (NFATc1) expression, thereby decreasing osteoclastogenesis-related marker gene expression, including tartrate-resistant acid phosphatase, osteoclast stimulatory transmembrane protein, cathepsin K, and matrix metallopeptidase 9. Curdlan inhibited RANKL-induced c-fos expression, followed by suppression of NFATc1 autoamplification, without significantly affecting the NF-κB signaling pathway. We also observed that curdlan treatment decreased Syk protein in d-RAWs. Inhibition of the dectin 1-Syk kinase pathway by Syk-specific siRNA or chemical inhibitors suppressed osteoclast formation and NFATc1 expression stimulated by RANKL. In conclusion, our results demonstrate that curdlan potentially inhibits osteoclast differentiation, especially NFATc1 expression, and that Syk kinase plays a crucial role in the transcriptional pathways. This suggests that the activation of dectin 1-Syk kinase interaction critically regulates the genes required for osteoclastogenesis.
Volume 289(27)
Pages 19191-203
Published 2014-7-4
DOI 10.1074/jbc.M114.551416
PII S0021-9258(20)40502-2
PMID 24821724
PMC PMC4081954
MeSH Active Transport, Cell Nucleus / drug effects Animals Bone Marrow Cells / cytology Bone Marrow Cells / drug effects Cell Line Cell Nucleus / drug effects Cell Nucleus / metabolism Dose-Response Relationship, Drug Enzyme Activation / drug effects Gene Expression Regulation / drug effects Intracellular Signaling Peptides and Proteins / metabolism* Lectins, C-Type / agonists* Lectins, C-Type / metabolism Male Mice NFATC Transcription Factors / antagonists & inhibitors* NFATC Transcription Factors / genetics Osteoclasts / cytology* Osteoclasts / drug effects* Osteoclasts / metabolism Protein-Tyrosine Kinases / metabolism* Proteolysis / drug effects RANK Ligand / pharmacology Syk Kinase beta-Glucans / chemistry beta-Glucans / pharmacology*
IF 4.238
Times Cited 12
Human and Animal Cells ST2(RCB0224) RAW 264(RCB0535)