Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Inflammopharmacology. 2024 Oct;32(5):3461-3474. doi: 10.1007/s10787-024-01552-6. Epub 2024 Aug 16.
Inflammatory diseases often result in bone loss due to persistent inflammation, which activates osteoclasts and increases bone resorption. Oxysophocarpine (OSC), a bioalkaloid extracted from the roots of Sophora japonica and other leguminous plants, has neuroprotective and anti-tumor properties. However, it is still uncertain whether OSC can effectively inhibit the differentiation of osteoclasts and bone resorption. Therefore, this study explored the potential role of OSC in osteoclast formation and inflammatory osteolysis and its underlying mechanisms.
This study involved inducing primary mouse bone marrow macrophages (BMMs) into osteoclasts using macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL) and examined the effects of OSC on osteoclast (OC) differentiation, function, and intracellular reactive oxygen species (ROS) production. The impact of OSC on the expression of osteoclast-specific genes and inflammation-related factors was assessed using real-time quantitative PCR. Additionally, changes in oxidative stress-related factors, NF-κB, and MAPK signaling pathways were examined using western blotting. Finally, this study investigated the influence of OSC on a mouse cranial bone resorption model induced by titanium (Ti) particles in vivo.
OSC inhibited OC differentiation and resorption and reduces intracellular ROS levels. Moreover, OSC suppressed IL-1β, TNF-α, IL-6, and osteoclast-specific gene transcription while increasing Nrf2 and HO-1 protein expression. Furthermore, OSC inhibited the expression and autoregulation of the NFATc1 gene, ultimately leading to a reduction in Ti particle-induced bone resorption in mice.
OSC could be regarded as an innovative medication for the treatment of osteoclast-associated inflammatory osteolytic diseases.
炎症性疾病常因持续的炎症而导致骨质流失，从而激活破骨细胞并增加骨吸收。氧化槐果碱（OSC）是从苦参和其他豆科植物的根部提取的生物生物碱，具有神经保护和抗肿瘤特性。然而，目前尚不清楚 OSC 是否能有效抑制破骨细胞分化和骨吸收。因此，本研究探讨了 OSC 在破骨细胞形成和炎症性骨溶解中的潜在作用及其潜在机制。
本研究通过巨噬细胞集落刺激因子（M-CSF）和核因子-κB 受体激活配体（RANKL）诱导原代小鼠骨髓巨噬细胞（BMMs）分化为破骨细胞，并观察 OSC 对破骨细胞（OC）分化、功能和细胞内活性氧（ROS）产生的影响。采用实时定量 PCR 检测 OSC 对破骨细胞特异性基因和炎症相关因子表达的影响。同时，通过 Western blot 检测氧化应激相关因子、NF-κB 和 MAPK 信号通路的变化。最后，本研究在体内研究了 OSC 对钛（Ti）颗粒诱导的小鼠颅骨骨吸收模型的影响。
OSC 抑制 OC 分化和吸收，并降低细胞内 ROS 水平。此外，OSC 抑制了白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和破骨细胞特异性基因的转录，同时增加了 Nrf2 和 HO-1 蛋白的表达。此外，OSC 抑制了 NFATc1 基因的表达和自身调节，最终导致小鼠 Ti 颗粒诱导的骨吸收减少。
OSC 可作为一种治疗与破骨细胞相关的炎症性骨溶解疾病的创新药物。
