Department of Orthopedics, Dongguan People's Hospital, Dongguan, Guangdong 523000, China.
Department of Orthopedics, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, China.
Biochem Pharmacol. 2019 May;163:279-289. doi: 10.1016/j.bcp.2019.02.002. Epub 2019 Feb 2.
Osteoporosis is a chronic bone lytic disease, because of inadequate bone ossification and/or excessive bone resorption. Even though drugs are currently available for the treatment of osteoporosis, there remains an unmet need for the development of more specific novel agents with less adverse effects. Dehydrocostus lactone (DHC), a natural sesquiterpene lactone, was previously found to affect the differentiation of inflammatory cells by inhibiting NF-κB pathways, and garnered much interest for its anti-cancer properties via SOCS-mediated cell cycle arrest and apoptosis. As NF-κB pathway plays an essential role in osteoclast differentiation, we sought to discover the biological effects of DHC on osteoclast differentiation and resorptive activity, as well as the underlying mechanisms on these effects. Our research found that DHC inhibited RANKL-induced osteoclast differentiation, bone resorption and osteoclast specific genes expression via suppression of NF-κB and NFAT signaling pathways in vitro. We further demonstrated that DHC protected against ovariectomy (OVX)-induced bone loss in mice and the protective effect was mediated at least in part through the attenuation of NF-κB signaling pathway. Thus, this study provides insight that DHC might be used as a potential pharmacological treatment for osteoporosis.
骨质疏松症是一种慢性溶骨性骨病，由于骨形成不足和/或骨吸收过度。尽管目前有药物可用于治疗骨质疏松症，但仍需要开发更具特异性、不良反应更少的新型药物。去氢木香内酯（DHC）是一种天然倍半萜内酯，先前的研究发现它通过抑制 NF-κB 通路影响炎症细胞的分化，因其通过 SOCS 介导的细胞周期阻滞和凋亡发挥抗癌特性而备受关注。由于 NF-κB 通路在破骨细胞分化中起着至关重要的作用，我们试图发现 DHC 对破骨细胞分化和吸收活性的生物学效应，以及这些效应的潜在机制。我们的研究发现，DHC 通过抑制 NF-κB 和 NFAT 信号通路，在体外抑制 RANKL 诱导的破骨细胞分化、骨吸收和破骨细胞特异性基因表达。我们进一步证明，DHC 可预防去卵巢（OVX）诱导的小鼠骨丢失，其保护作用至少部分是通过减轻 NF-κB 信号通路介导的。因此，这项研究提供了一些见解，即 DHC 可能被用作治疗骨质疏松症的潜在药理学治疗方法。
