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HERO ID
6996490
Reference Type
Journal Article
Title
Celecoxib inhibits osteoblast maturation by suppressing the expression of Wnt target genes
Author(s)
Nagano, A; Arioka, M; Takahashi-Yanaga, F; Matsuzaki, E; Sasaguri, T; ,
Year
2017
Is Peer Reviewed?
Yes
Journal
Journal of Pharmacological Sciences
ISSN:
1347-8613
EISSN:
1347-8648
Publisher
JAPANESE PHARMACOLOGICAL SOC
Location
KYOTO
Page Numbers
18-24
Language
English
PMID
28007462
DOI
10.1016/j.jphs.2016.11.003
Web of Science Id
WOS:000396509600003
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to impair bone healing. We previously reported that in colon cancer cells, celecoxib, a COX-2-selective NSAID, inhibited the canonical Wnt/β-catenin signaling pathway. Since this pathway also plays an important role in osteoblast growth and differentiation, we examined the effect of celecoxib on maturation of osteoblast-like cell line MC3T3-E1. Celecoxib induced degradation of transcription factor 7-like 2, a key transcription factor of the canonical Wnt pathway. Subsequently, we analyzed the effect of celecoxib on two osteoblast differentiation markers; runt-related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP), both of which are the products of the canonical Wnt pathway target genes. Celecoxib inhibited the expression of both RUNX2 and ALP by suppressing their promoter activity. Consistent with these observations, celecoxib also strongly inhibited osteoblast-mediated mineralization. These results suggest that celecoxib inhibits osteoblast maturation by suppressing Wnt target genes, and this could be the mechanism that NSAIDs inhibit bone formation and fracture healing.
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