Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Orthopedic Research Institute of Zhejiang University, Hangzhou, China.
J Cell Mol Med. 2019 Aug;23(8):5762-5770. doi: 10.1111/jcmm.14492. Epub 2019 Jun 21.
Osteolysis is characterized by overactivated osteoclast formation and potent bone resorption. It is enhanced in many osteoclast-related diseases including osteoporosis and periprosthetic osteolysis. The shortage of effective treatments for these pathological processes emphasizes the importance of screening and identifying potential regimens that could attenuate the formation and function of osteoclasts. Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone containing anti-inflammatory properties. Here, we showed that DHE suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and osteoclast marker gene expression. It also inhibited F-actin ring formation and bone resorption in a dose-dependent manner in vitro. Moreover, DHE inhibited the RANKL-induced phosphorylation of NF-κB, mitigated bone erosion in vivo in lipopolysaccharide-induced inflammatory bone loss model and particle-induced calvarial osteolysis model. Together, these results suggest that DHE reduces osteoclast-related bone loss via the modulation of NF-κB activation during osteoclastogenesis indicating that it might be a useful treatment for osteoclast-related skeletal disorders.
骨溶解的特征为破骨细胞过度激活形成和强效的骨质吸收。它在许多与破骨细胞相关的疾病中增强，包括骨质疏松症和人工关节周围骨溶解。这些病理过程缺乏有效治疗方法，强调了筛选和鉴定可能减轻破骨细胞形成和功能的潜在方案的重要性。去氢木香内酯（DHE）是一种具有抗炎特性的天然倍半萜内酯。在这里，我们表明 DHE 抑制核因子-κB 配体（RANKL）诱导的破骨细胞形成和破骨细胞标记基因表达。它还在体外以剂量依赖性方式抑制 F-肌动蛋白环形成和骨质吸收。此外，DHE 抑制 RANKL 诱导的 NF-κB 磷酸化，减轻脂多糖诱导的炎症性骨丢失模型和颗粒诱导的颅盖骨骨溶解模型中的骨侵蚀。总之，这些结果表明 DHE 通过调节破骨细胞形成过程中的 NF-κB 激活来减少与破骨细胞相关的骨丢失，表明它可能是治疗与破骨细胞相关的骨骼疾病的有用方法。
