RRC ID 39182
著者 Hasegawa S, Kitoh H, Ohkawara B, Mishima K, Matsushita M, Masuda A, Ishiguro N, Ohno K.
タイトル Tranilast stimulates endochondral ossification by upregulating SOX9 and RUNX2 promoters.
ジャーナル Biochem Biophys Res Commun
Abstract Endochondral ossification is an essential process for reparative phase of fracture healing, which starts with the differentiation of mesenchymal cells into chondrocytes followed by substitution of bone tissue. It is strictly controlled by the expression of crucial transcriptional factors: SOX9 in the early phase and RUNX2 in the late phase. Screening of FDA-approved compounds revealed that an anti-allergic drug, tranilast, that has been used for more than 30 years in clinical practice, enhanced the SOX9 promoter in chondrogenic cells and the RUNX2 promoter in osteoblastic cells. We observed that tranilast increased mRNA expression of both Sox9 and Runx2 in differentiating ATDC5 chondrogenic progenitor cells. Tranilast upregulated mRNA expression of chondrogenic marker genes (Col2a1, Acan, Col10a1, and Mmp13) in differentiating ATDC5 cells. Moreover, tranilast upregulated mRNA expression of essential signaling molecules involved in endochondral ossification (Pthrp, Ihh, and Axin2). In the later phase of differentiation of ATDC5 cells, tranilast increased synthesis of matrix proteoglycans, induced the alkaline phosphatase activity, and tended to accelerate mineralization. Tranilast is a potential agent that accelerates fracture repair by promoting the regulatory steps of endochondral ossification.
巻・号 470(2)
ページ 356-361
公開日 2016-2-5
DOI 10.1016/j.bbrc.2016.01.044
PII S0006-291X(16)30044-4
PMID 26777999
MeSH Animals Cell Line Chondrogenesis / drug effects Chondrogenesis / physiology* Core Binding Factor Alpha 1 Subunit / metabolism* Fracture Healing / drug effects Mice Osteogenesis / drug effects Osteogenesis / physiology* SOX9 Transcription Factor / metabolism* Up-Regulation / drug effects Up-Regulation / physiology ortho-Aminobenzoates / administration & dosage*
IF 2.985
引用数 1
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY BIOPHYSICS
リソース情報
ヒト・動物細胞 10T1/2(RCB0247)