title: Toddaculin, Isolated from of Toddalia asiatica (L.) Lam., Inhibited Osteoclastogenesis in RAW 264 Cells and Enhanced Osteoblastogenesis in MC3T3-E1 Cells.
abstract: Osteoporosis with bone loss is widely recognized as a major health problem. Bone homeostasis is maintained by balancing bone formation and bone resorption. The imbalance caused by increased bone resorption over bone formation can lead to various bone-related diseases such as osteoporosis and rheumatoid arthritis. Osteoclasts are the principal cells responsible for bone resorption and the main targets of anti-resorptive therapies. However, excessive inhibition of osteoclast differentiation may lead to inhibition of osteoblast differentiation. Therefore, it is important to screen for new compounds capable of inhibiting bone resorption and enhancing bone formation. Toddalia asiatica (L.) Lam. has been utilized traditionally for medicinal purposes such as the treatment of rheumatism. Currently, the extract is considered to be a good source of pharmacological agents for the treatment of bone-related diseases, but the active compounds have yet to be identified. We investigated whether toddaculin, derived from Toddalia asiatica (L.) Lam., affects both processes by inhibiting bone resorption and enhancing bone formation. Towards this end, we used pre-osteoclastic RAW 264 cells and pre-osteoblastic MC3T3-E1 cells. We found that toddaculin not only inhibited the differentiation of osteoclasts via activation of the NF-κB, ERK 1/2, and p38 MAPK signaling pathways, but it also induced differentiation and mineralization of osteoblasts by regulating differentiation factors. Thus, toddaculin might be beneficial for the prevention and treatment of osteoporosis.
authors.affiliation: Food Function Research Team, Saito Laboratory, Japan Food Research Laboratories, Ibaraki, Osaka, Japan; Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Food Function Research Team, Saito Laboratory, Japan Food Research Laboratories, Ibaraki, Osaka, Japan.
authors.forename: Momochika
authors.initials: M
authors.lastname: Kumagai
authors.affiliation: Food Function Research Team, Saito Laboratory, Japan Food Research Laboratories, Ibaraki, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mishima
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Ito
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Yurika
authors.initials: Y
authors.lastname: Otoki
authors.affiliation: Food Function Research Team, Saito Laboratory, Japan Food Research Laboratories, Ibaraki, Osaka, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Harada
authors.affiliation: Section of Applied Testing, Tama Laboratory, Japan Food Research Laboratories, Tama, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Section of Nutraceutical Analysis, Saito Laboratory, Japan Food Research Laboratories, Ibaraki, Osaka, Japan.
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Section of Biological Safety Research, Tama Laboratory, Japan Food Research Laboratories, Tama, Tokyo, Japan.
authors.forename: Misora
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Food Function Research Team, Saito Laboratory, Japan Food Research Laboratories, Ibaraki, Osaka, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Yoshida
authors.affiliation: Food Function Research Team, Saito Laboratory, Japan Food Research Laboratories, Ibaraki, Osaka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Food Function Research Team, Saito Laboratory, Japan Food Research Laboratories, Ibaraki, Osaka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Watai
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Miyazawa
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003374:Coumarins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects*; D010010:Osteoclasts / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D003374:Coumarins; D010936:Plant Extracts; C576564:toddaculin