A novel osteogenic helioxanthin-derivative acts in a BMP-dependent manner.
To effectively treat serious bone defects using bone regenerative medicine, there is a need for the development of a small chemical compound that potently induces bone formation. We now report a novel osteogenic helioxanthin-derivative, TH. TH induced osteogenic differentiation in MC3T3-E1 cells, mouse primary osteoblasts, and mouse embryonic stem cells. The combination of TH and bone morphogenetic protein (BMP) 2 induced the mRNA expression of osteoblast marker genes and calcification in primary fibroblasts. The TH induced the mRNA of the inhibitor of DNA-binding 1 (Id-1), and its osteogenic effect was inhibited by Smad6 or Noggin. Furthermore, TH induced the mRNA expression of Bmp4 and Bmp6. These data suggest that TH exerts its potent osteogenic effect in a BMP-dependent manner by enhancing the effects of the existing BMPs and/or increasing the expression of Bmp4 and Bmp6. TH may help establish a more efficient bone regeneration system.
Ohba
Shinsuke
S
Division of Sensory and Motor System Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Nakajima
Keiji
K
Komiyama
Yusuke
Y
Kugimiya
Fumitaka
F
Igawa
Kazuyo
K
Itaka
Keiji
K
Moro
Toru
T
Nakamura
Kozo
K
Kawaguchi
Hiroshi
H
Takato
Tsuyoshi
T
Chung
Ung-il
UI
D016475:3T3 Cells; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D017705:Lignans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D014970:Xanthines / Q000008:administration & dosage*
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004338:Drug Combinations; D017705:Lignans; D016212:Transforming Growth Factor beta; D014970:Xanthines; C505802:helioxanthin