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

doi:10.1016/j.heliyon.2023.e13080

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

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

Authors

Ruijia Yang^{1

2}, Yanjing Guo^{1

3}, Sujing Zong^{1

3}, Zhou Ma¹, Zhenyu Wang¹, Jiyu Zhao¹, Jinmei Yang⁴, Liping Li³, Chongwei Chen¹, Shaowei Wang^{1

3}

Affiliations

¹ Shanxi Key Lab of Bone and Soft Tissue Injury Repair, Department of Orthopaedics, The Second Hospital of Shanxi Medical University, Taiyuan, China.
² Department of Laboratory Medicine, Southern Central Hospital of Yunnan Province (The First People's Hospital of Honghe State), Mengzi, China.
³ Department of Biochemistry, Basic Medical College, Shanxi Medical University, Taiyuan, China.
⁴ Department of Pediatrics, Southern Central Hospital of Yunnan Province (The First People's Hospital of Honghe State), Mengzi, China.

Abstract

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.

Keywords: Bardoxolone methyl; NF-κB; Nrf2/HO-1; Osteoarthritis; Osteoclast.