TAK-778, a novel synthetic 3-benzothiepin derivative, promotes chondrogenesis in vitro and in vivo.
TAK-778, a novel synthetic 3-benzothiepin derivative, stimulates the formation of cartilaginous nodules in mouse chondroprogenitor-like ATDC5 cells in vitro in association with upregulation of the gene expression of transforming growth factor-beta(2), but not bone morphogenetic protein-4 and insulin-like growth factor-I. One-shot injection of the TAK-778-containing sustained-release microcapsules accelerated the repair process of the full thickness defects of articular cartilage in rabbit knees. Our in vitro and in vivo results indicate that TAK-778 may be a therapeutically useful synthetic agent for articular cartilage repair.
Akiyama
H
H
Department of Nuclear Medicine and Diagnostic Imaging, Kyoto University, Kyoto, Sakyo, 606-8507, Japan. akiy@kuhp.kyoto-u.ac.jp
Fukumoto
A
A
Shigeno
C
C
Ito
H
H
Mukai
S
S
Hoshino
T
T
Makino
H
H
Nakamura
T
T
D000818:Animals; D001582:Benzothiepins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D002214:Capsules; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D020219:Chondrogenesis / Q000187:drug effects*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D051379:Mice; D011509:Proteoglycans / Q000032:analysis; D011817:Rabbits; D013194:Staining and Labeling; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics
D001582:Benzothiepins; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002214:Capsules; D003692:Delayed-Action Preparations; D011509:Proteoglycans; C120450:TAK 778; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I