RRC ID 52083
Author Chaweewannakorn W, Ariyoshi W, Okinaga T, Morikawa K, Saeki K, Maki K, Nishihara T.
Title Ameloblastin and enamelin prevent osteoclast formation by suppressing RANKL expression via MAPK signaling pathway.
Journal Biochem Biophys Res Commun
Abstract Ameloblastin (Ambn) and enamelin (Enam) play a pivotal role in enamel mineralization. Previous studies have demonstrated that these enamel-related gene products also affect bone growth and remodeling; however, the underlying mechanisms have not been elucidated. In the present study, we examined the effects of Ambn and Enam on the receptor activator of nuclear factor kappa-B ligand (RANKL) expression induced with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and dexamethasone (DEX) on mouse bone marrow stromal cell line ST2 cells. We then verified the effect of Ambn and Enam on osteoclastogenesis. We found that pretreatment with recombinant human Ambn (rhAmbn) and recombinant human Enam (rhEnam) remarkably suppressed RANKL mRNA and protein expression induced with 1,25(OH)2D3 and DEX. Interestingly, rhAmbn and rhEnam attenuated the phosphorylation of mitogen-activated protein kinases (MAPK), including ERK1/2, JNK, and p38 in ST2 cells stimulated with 1,25(OH)2D3 and DEX. Moreover, pretreatment with specific inhibitors of ERK1/2 and p38, but not JNK, blocked RANKL mRNA and protein expression. Cell co-culture results showed that rhAmbn and rhEnam downregulated mouse bone marrow cell differentiation into osteoclasts induced with 1,25(OH)2D3 and DEX-stimulated ST2 cells. These results suggest that Ambn and Enam may indirectly suppress RANKL-induced osteoclastogenesis via downregulation of p38 and ERK1/2 MAPK signaling pathways in bone marrow stromal cells.
Volume 485(3)
Pages 621-626
Published 2017-4-8
DOI 10.1016/j.bbrc.2017.01.181
PII S0006-291X(17)30256-5
PMID 28161637
MeSH Animals Blotting, Western Bone Marrow Cells / cytology Bone Marrow Cells / drug effects Bone Marrow Cells / metabolism Calcitriol / pharmacology Cell Differentiation / drug effects Cell Differentiation / genetics Cell Line Cells, Cultured Coculture Techniques Dental Enamel Proteins / genetics Dental Enamel Proteins / pharmacology* Dexamethasone / pharmacology Extracellular Matrix Proteins / genetics Extracellular Matrix Proteins / pharmacology* Gene Expression / drug effects Glucocorticoids / pharmacology Humans MAP Kinase Signaling System / drug effects* Male Mesenchymal Stem Cells / drug effects Mesenchymal Stem Cells / metabolism Mice Osteoclasts / drug effects* Osteoclasts / metabolism Osteogenesis / drug effects Osteogenesis / genetics RANK Ligand / genetics RANK Ligand / metabolism* Recombinant Proteins / pharmacology Reverse Transcriptase Polymerase Chain Reaction Vitamins / pharmacology
IF 2.705
Times Cited 5
Human and Animal Cells ST2(RCB0224)