Watanabe Akio, Kumagai Momochika, Mishima Takashi, Ito Junya, Otoki Yurika, Harada Teppei, Kato Tsuyoshi, Yoshida Mikihiko, Suzuki Misora, Yoshida Izumi, Fujita Kazuhiro, Watai Masatoshi, Nakagawa Kiyotaka, Miyazawa Teruo
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.
Food Function Research Team, Saito Laboratory, Japan Food Research Laboratories, Ibaraki, Osaka, Japan.
PLoS One. 2015 May 18;10(5):e0127158. doi: 10.1371/journal.pone.0127158. eCollection 2015.
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.
伴有骨质流失的骨质疏松症被广泛认为是一个主要的健康问题。骨稳态通过平衡骨形成和骨吸收来维持。骨吸收超过骨形成所导致的失衡会引发各种与骨相关的疾病，如骨质疏松症和类风湿性关节炎。破骨细胞是负责骨吸收的主要细胞，也是抗吸收疗法的主要靶点。然而，过度抑制破骨细胞分化可能会导致成骨细胞分化受到抑制。因此，筛选能够抑制骨吸收并增强骨形成的新化合物具有重要意义。飞龙掌血（Toddalia asiatica (L.) Lam.）传统上一直被用于药用，比如治疗风湿病。目前，其提取物被认为是治疗骨相关疾病的良好药物来源，但其中的活性化合物尚未得到鉴定。我们研究了源自飞龙掌血的托达库林是否通过抑制骨吸收和增强骨形成来影响这两个过程。为此，我们使用了前破骨细胞RAW 264细胞和前成骨细胞MC3T3-E1细胞。我们发现托达库林不仅通过激活NF-κB、ERK 1/2和p38 MAPK信号通路来抑制破骨细胞的分化，还通过调节分化因子来诱导成骨细胞的分化和矿化。因此，托达库林可能对骨质疏松症的预防和治疗有益。
