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Ameloblastin and enamelin prevent osteoclast formation by suppressing RANKL expression via MAPK signaling pathway.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2017 Apr 08; Vol. 485 (3), pp. 621-626. Date of Electronic Publication: 2017 Feb 02. - Publication Year :
- 2017
-
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 D <subscript>3</subscript> (1,25(OH) <subscript>2</subscript> D <subscript>3</subscript> ) 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) <subscript>2</subscript> D <subscript>3</subscript> 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) <subscript>2</subscript> D <subscript>3</subscript> 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) <subscript>2</subscript> D <subscript>3</subscript> 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.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- 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
Dexamethasone pharmacology
Extracellular Matrix Proteins genetics
Gene Expression drug effects
Glucocorticoids pharmacology
Humans
Male
Mesenchymal Stem Cells drug effects
Mesenchymal Stem Cells metabolism
Mice
Osteoclasts metabolism
Osteogenesis drug effects
Osteogenesis genetics
RANK Ligand genetics
Recombinant Proteins pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Vitamins pharmacology
Dental Enamel Proteins pharmacology
Extracellular Matrix Proteins pharmacology
MAP Kinase Signaling System drug effects
Osteoclasts drug effects
RANK Ligand metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 485
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 28161637
- Full Text :
- https://doi.org/10.1016/j.bbrc.2017.01.181