| RRC ID |
41742
|
| 著者 |
Kuriyama K, Higuchi C, Tanaka K, Yoshikawa H, Itoh K.
|
| タイトル |
A novel anti-rheumatic drug, T-614, stimulates osteoblastic differentiation in vitro and bone morphogenetic protein-2-induced bone formation in vivo.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
T-614 (N-[3-(formylamino)-4-oxo-6-phenoxy-4H-chromen-7-yl]methanesulfonamide), a newly developed anti-rheumatic drug under clinical trial, is an anti-inflammatory agent which has been reported to show the inhibitory effect of bone destruction in vivo arthritis model. We found that T-614 stimulated osteoblastic differentiation of stromal cell line (ST2) and preosteoblastic cell line (MC3T3-E1) in the presence or absence of recombinant human bone morphogenetic protein-2 (rhBMP-2). Calcium content of mineralized nodules was 14-fold elevated by the addition of T-614 in the presence of rhBMP-2 in ST2 but not MC3T3-E1. Oral administration of T-614 to mice also promoted rhBMP-2 induced bone formation in vivo. Northern blot analysis showed that transcriptional level of osterix, an essential transcription factor for osteoblastic differentiation, was 3-fold increased by T-614 with rhBMP-2 in ST2. Taken together, these results suggested that T-614 possessed anabolic effects on bone metabolism, besides suppressor of bone resorption, by increased expression of osterix.
|
| 巻・号 |
299(5)
|
| ページ |
903-9
|
| 公開日 |
2002-12-20
|
| DOI |
10.1016/s0006-291x(02)02754-7
|
| PII |
S0006291X02027547
|
| PMID |
12470665
|
| MeSH |
Alkaline Phosphatase / analysis
Alkaline Phosphatase / metabolism
Animals
Antirheumatic Agents / metabolism
Antirheumatic Agents / pharmacology*
Benzopyrans / metabolism
Benzopyrans / pharmacology*
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins / pharmacology*
Bone and Bones / anatomy & histology
Bone and Bones / drug effects
Cell Differentiation / drug effects
Cell Line
Dose-Response Relationship, Drug
Drug Synergism
Mice
Neoplasm Proteins*
Osteoblasts / cytology
Osteoblasts / drug effects*
Osteoblasts / physiology
Osteocalcin / genetics
Osteocalcin / metabolism
Osteogenesis / drug effects*
RNA, Messenger / biosynthesis
Stromal Cells / drug effects
Stromal Cells / metabolism
Sulfonamides / metabolism
Sulfonamides / pharmacology*
Transcription Factors / biosynthesis
Transcription Factors / genetics
Transforming Growth Factor beta*
|
| IF |
2.985
|
| 引用数 |
24
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MC3T3-E1(RCB1126)
ST2(RCB0224) |
