RRC ID 52333
Author Kusuyama J, Kamisono A, ChangHwan S, Amir MS, Bandow K, Eiraku N, Ohnishi T, Matsuguchi T.
Title Spleen tyrosine kinase influences the early stages of multilineage differentiation of bone marrow stromal cell lines by regulating phospholipase C gamma activities.
Journal J Cell Physiol
Abstract Bone marrow stromal cells (BMSCs) are multipotent cells that can differentiate into adipocytes and osteoblasts. Inadequate BMSC differentiation is occasionally implicated in chronic bone metabolic disorders. However, specific signaling pathways directing BMSC differentiation have not been elucidated. Here, we explored the roles of spleen tyrosine kinase (Syk) in BMSC differentiation into adipocytes and osteoblasts. We found that Syk phosphorylation was increased in the early stage, whereas its protein expression was gradually decreased during the adipogenic and osteogenic differentiation of two mouse mesenchymal stromal cell lines, ST2 and 10T(1/2), and a human BMSC line, UE6E-7-16. Syk inactivation with either a pharmacological inhibitor or Syk-specific siRNA suppressed adipogenic differentiation, characterized by decreased lipid droplet appearance and the gene expression of fatty acid protein 4 (Fabp4), peroxisome proliferator-activated receptor γ2 (Pparg2), CCAAT/enhancer binding proteins α (C/EBPα), and C/EBPβ. In contrast, Syk inhibition promoted osteogenic differentiation, represented by increase in matrix mineralization and alkaline phosphatase (ALP) activity, as well as the expression levels of osteocalcin, runt-related transcription factor 2 (Runx2), and distal-less homeobox 5 (Dlx5) mRNAs. We also found that Syk-induced signals are mediated by phospholipase C γ1 (PLCγ1) in osteogenesis and PLCγ2 in adipogenesis. Notably, Syk-activated PLCγ2 signaling was partly modulated through B-cell linker protein (BLNK) in adipogenic differentiation. On the other hand, growth factor receptor-binding protein 2 (Grb2) was involved in Syk-PLCγ1 axis in osteogenic differentiation. Taken together, these results indicate that Syk-PLCγ signaling has a dual role in regulating the initial stage of adipogenic and osteogenic differentiation of BMSCs.
Volume 233(3)
Pages 2549-2559
Published 2018-3-1
DOI 10.1002/jcp.26130
PMID 28786489
MeSH Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism Adipocytes / enzymology* Adipogenesis* Animals Biomarkers / metabolism Cell Line Cell Lineage* GRB2 Adaptor Protein / genetics GRB2 Adaptor Protein / metabolism Gene Expression Regulation Humans Mesenchymal Stem Cells / enzymology* Mice, Inbred C3H Osteoblasts / enzymology* Osteogenesis* Phenotype Phospholipase C gamma / genetics Phospholipase C gamma / metabolism* Phosphorylation RNA Interference RNA, Messenger / genetics RNA, Messenger / metabolism Signal Transduction Syk Kinase / genetics Syk Kinase / metabolism* Time Factors Transfection
IF 4.522
Human and Animal Cells ST2(RCB0224)