Bardoxolone methyl ameliorates osteoarthritis by inhibiting osteoclastogenesis and protecting the extracellular matrix against degradation
Ruijia Yang,
Yanjing Guo,
Sujing Zong,
Zhou Ma,
Zhenyu Wang,
Jiyu Zhao,
Jinmei Yang,
Liping Li,
Chongwei Chen,
Shaowei Wang
Affiliations
Ruijia Yang
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
Yanjing Guo
Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China; Department of Biochemistry, Basic Medical College, Shanxi Medical University, Taiyuan, China
Sujing Zong
Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China; Department of Biochemistry, Basic Medical College, Shanxi Medical University, Taiyuan, China
Zhou Ma
Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China
Zhenyu Wang
Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China
Jiyu Zhao
Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China
Jinmei Yang
Department of Pediatrics, Southern Central Hospital of Yunnan Province (The First People's Hospital of Honghe State), Mengzi, China
Liping Li
Department of Biochemistry, Basic Medical College, Shanxi Medical University, Taiyuan, China
Chongwei Chen
Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China; Corresponding authors. Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Shaowei Wang
Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China; Department of Biochemistry, Basic Medical College, Shanxi Medical University, Taiyuan, China; Corresponding authors. Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China.
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.
