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Regulatory effects of fibroblast growth factor-8 and tumor necrosis factor-α on osteoblast marker expression induced by bone morphogenetic protein-2.
- Source :
-
Peptides [Peptides] 2015 Nov; Vol. 73, pp. 88-94. Date of Electronic Publication: 2015 Sep 26. - Publication Year :
- 2015
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Abstract
- BMP induces osteoblast differentiation, whereas a key proinflammatory cytokine, TNF-α, causes inflammatory bone damage shown in rheumatoid arthritis. FGF molecules are known to be involved in bone homeostasis. However, the effects of FGF-8 on osteoblast differentiation and the interaction between FGF-8, BMPs and TNF-α have yet to be clarified. Here we investigated the effects of FGF-8 in relation to TNF-α actions on BMP-2-induced osteoblast marker expression using myoblast cell line C2C12, osteoblast precursor cell line MC3T3-E1 and rat calvarial osteoblasts. It was revealed that FGF-8 inhibited BMP-2-induced expression of osteoblast differentiation markers, including Runx2, osteocalcin, alkaline phosphatase, type-1 collagen and osterix, in a concentration-dependent manner. The inhibitory effects of FGF-8 on BMP-induced osteoblast differentiation and Smad1/5/8 activation were enhanced in the presence of TNF-α action. FGF-8 also inhibited BMP-2-induced expression of Wnt5a, which activates a non-canonical Wnt signaling pathway. FGF-8 had no significant influence on the expression levels of TNF receptors, while FGF-8 suppressed the expression of inhibitory Smad6 and Smad7, suggesting a possible feedback activity through FGF to BMP receptor (BMPR) signaling. Of note, inhibition of ERK activity and FGF receptor (FGFR)-dependent protein kinase, but not JNK or NFκB pathway, suppressed the FGF-8 actions on BMP-induced osteoblast differentiation. FGF-8 was revealed to suppress BMP-induced osteoblast differentiation through the ERK pathway and the effects were enhanced by TNF-α. Given the finding that FGF-8 expression was increased in synovial tissues of rheumatoid arthritis, the functional interaction between FGFR and BMPR signaling may be involved in the development process of inflammatory bone damage.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Bone Morphogenetic Protein 2 pharmacology
Cell Differentiation drug effects
Cell Differentiation physiology
Cell Line
Fibroblast Growth Factor 8 pharmacology
Humans
MAP Kinase Kinase 4 metabolism
MAP Kinase Signaling System drug effects
Mice
NF-kappa B metabolism
Osteoblasts cytology
Rats
Smad Proteins metabolism
Antigens, Differentiation biosynthesis
Bone Morphogenetic Protein 2 metabolism
Fibroblast Growth Factor 8 metabolism
MAP Kinase Signaling System physiology
Osteoblasts metabolism
Tumor Necrosis Factor-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-5169
- Volume :
- 73
- Database :
- MEDLINE
- Journal :
- Peptides
- Publication Type :
- Academic Journal
- Accession number :
- 26409788
- Full Text :
- https://doi.org/10.1016/j.peptides.2015.09.007