巴多昔芬甲酯通过抑制破骨细胞生成和保护细胞外基质免受降解来改善骨关节炎。

Bardoxolone methyl ameliorates osteoarthritis by inhibiting osteoclastogenesis and protecting the extracellular matrix against degradation.

作者信息

Yang Ruijia, Guo Yanjing, Zong Sujing, Ma Zhou, Wang Zhenyu, Zhao Jiyu, Yang Jinmei, Li Liping, Chen Chongwei, Wang Shaowei

机构信息

Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Department of Laboratory Medicine, Southern Central Hospital of Yunnan Province (The First People's Hospital of Honghe State), Mengzi, China.

出版信息

Heliyon. 2023 Jan 20;9(2):e13080. doi: 10.1016/j.heliyon.2023.e13080. eCollection 2023 Feb.

Inflammation and oxidative damage are closely related to the development of osteoarthritis. Bardoxolone methyl (CDDO-Me), a semisynthetic oleanane triterpenoid, plays a strong anti-inflammatory and antioxidant role. The purpose of our research was to explore fundamental mechanisms of CDDO-Me in orthopaedics development. The results showed that CDDO-Me inhibited nuclear factor-κB ligand (RANKL)-induced osteoclast formation and extracellular matrix (ECM) degradation by activating the Nrf2/HO-1 signaling pathways and inhibiting NF-κB pathway activation and excess ROS production. In vivo, CDDO-Me significantly attenuated articular cartilage proteoglycan loss and the number of TRAP-positive osteoclasts in a destabilized medial meniscus (DMM) mouse model of OA. Taken together, these data demonstrate that CDDO-Me inhibits osteoclastogenesis and ECM degradation, underscoring its potential therapeutic value in treating OA.

炎症和氧化损伤与骨关节炎的发展密切相关。巴多昔芬甲酯（CDDO-Me）是一种半合成的齐墩果烷三萜类化合物，具有强大的抗炎和抗氧化作用。我们研究的目的是探索CDDO-Me在骨科疾病发展中的基本机制。结果表明，CDDO-Me通过激活Nrf2/HO-1信号通路、抑制NF-κB通路激活和过量ROS产生，抑制核因子κB配体（RANKL）诱导的破骨细胞形成和细胞外基质（ECM）降解。在体内，在骨关节炎的内侧半月板不稳定（DMM）小鼠模型中，CDDO-Me显著减轻了关节软骨蛋白聚糖的损失和抗酒石酸酸性磷酸酶（TRAP）阳性破骨细胞的数量。综上所述，这些数据表明CDDO-Me抑制破骨细胞生成和ECM降解，突出了其在治疗骨关节炎方面的潜在治疗价值。