RRC ID 61400
Author Tsubaki M, Satou T, Itoh T, Imano M, Yanae M, Kato C, Takagoshi R, Komai M, Nishida S.
Title Bisphosphonate- and statin-induced enhancement of OPG expression and inhibition of CD9, M-CSF, and RANKL expressions via inhibition of the Ras/MEK/ERK pathway and activation of p38MAPK in mouse bone marrow stromal cell line ST2.
Journal Mol Cell Endocrinol
Abstract Osteoclast differentiation is influenced by receptor activator of the NF-κB ligand (RANKL), macrophage colony-stimulating factor (M-CSF), and CD9, which are expressed on bone marrow stromal cells and osteoblasts. In addition, osteoprotegerin (OPG) is known as an osteoclastogenesis inhibitory factor. In this study, we investigated whether bisphosphonates and statins increase OPG expression and inhibit the expression of CD9, M-CSF, and RANKL in the bone marrow-derived stromal cell line ST2. We found that bisphosphonates and statins enhanced OPG mRNA expression and inhibited the expression of CD9, M-CSF, and RANKL mRNA. Futhermore, bisphosphonates and statins decreased the membrane localization of Ras and phosphorylated ERK1/2, and activated the p38MAPK. This indicates that bisphosphonates and statins enhanced OPG expression, and inhibited the expression of CD9, M-CSF, and RANKL through blocking the Ras/ERK pathway and activating p38MAPK. Accordingly, we believe that its clinical applications will be investigated in the future for the development of osteoporosis therapy.
Volume 361(1-2)
Pages 219-31
Published 2012-9-25
DOI 10.1016/j.mce.2012.05.002
PII S0303-7207(12)00268-7
PMID 22579611
MeSH Animals Bone Marrow Cells / drug effects Bone Marrow Cells / enzymology* Cell Death / drug effects Cell Line Cell Membrane / drug effects Cell Membrane / metabolism Cytoplasm / drug effects Cytoplasm / metabolism Diphosphonates / pharmacology* Enzyme Activation / drug effects Gene Expression Regulation / drug effects Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology* MAP Kinase Signaling System / drug effects Macrophage Colony-Stimulating Factor / genetics Macrophage Colony-Stimulating Factor / metabolism* Mice Osteoprotegerin / genetics Osteoprotegerin / metabolism* Phosphorylation / drug effects Protein Kinase Inhibitors / pharmacology Protein Prenylation / drug effects RANK Ligand / metabolism* RNA, Messenger / genetics RNA, Messenger / metabolism Stromal Cells / drug effects Stromal Cells / enzymology Tetraspanin 29 / genetics Tetraspanin 29 / metabolism* p38 Mitogen-Activated Protein Kinases / metabolism ras Proteins / antagonists & inhibitors ras Proteins / metabolism rho GTP-Binding Proteins / metabolism
IF 3.871
Human and Animal Cells ST2(RCB0224)