Celecoxib inhibits osteoblast maturation by suppressing the expression of Wnt target genes

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• 作者：Akihiro Nagano^a ; ^b ; ¹ ; Masaki Arioka^a ; ¹ ; Fumi Takahashi-Yanaga^a ; ^c ; ^{yanaga@clipharm.med.kyushu-u.ac.jp} ; Etsuko Matsuzaki^b ; ^d ; Toshiyuki Sasaguri^a
• 关键词：Osteoblast ; Celecoxib ; Wnt/β-catenin signaling pathway ; Mineralization ; Fracture healing
• 刊名：Journal of Pharmacological Sciences
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：133
• 期：1
• 页码：18-24
• 全文大小：1134 K
• 卷排序：133

文摘

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.