Department of Orthopedic, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, China.
Enze Medical Research Center, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, China.
J Cell Physiol. 2018 Sep;233(9):7067-7079. doi: 10.1002/jcp.26508. Epub 2018 Mar 25.
Balanced bone resorption and bone formation are vital for bone homeostasis. Excessive osteoclastic bone resorption in this process can cause a variety of bone disorders including osteoporosis, aseptic prosthetic loosening and tumor associated bone destruction. Bulleyaconitine A (BLA) is a natural compound that has been widely used for pain treatment but its role in osteolysis has not yet been investigated. In this study, we verified for the first time that BLA inhibited osteoclast formation, the mRNA expression of osteoclast-related genes and osteoclastic bone resorption by inhibiting NF-κB signal pathway and downstream NFATc1 expression. Meanwhile, BLA had a stimulatory effect in osteoblast differentiation and mineralization. Furthermore, BLA showed preventive effect in Ti particle-induced osteolysis model in vivo. Together, all our data demonstrated that BLA suppressed osteoclastogenesis and promoted osteoblastogenesis via suppressing NF-κB signal pathway and could be an alternative therapeutic choice against bone loss.
平衡的骨吸收和骨形成对于骨稳态至关重要。在这个过程中，破骨细胞的过度骨吸收会导致各种骨疾病，包括骨质疏松症、无菌性假体松动和肿瘤相关的骨破坏。乌头碱 A（BLA）是一种天然化合物，已广泛用于疼痛治疗，但它在骨溶解中的作用尚未得到研究。在这项研究中，我们首次验证了 BLA 通过抑制 NF-κB 信号通路和下游 NFATc1 的表达，抑制破骨细胞的形成、破骨细胞相关基因的 mRNA 表达和破骨细胞的骨吸收。同时，BLA 对成骨细胞的分化和矿化具有促进作用。此外，BLA 在体内钛颗粒诱导的骨溶解模型中表现出预防作用。总之，我们所有的数据表明，BLA 通过抑制 NF-κB 信号通路抑制破骨细胞生成并促进成骨细胞生成，可作为治疗骨丢失的一种替代选择。
