Targeting DDX6 attenuates osteoarthritis progression by inhibiting CPEB1-mediated ferroptosis in subchondral bone
Yonghui Zhou, Chong Li, Hao Wang, Meng Li, Yiqun Pang, Wei Xu, Baoliang Lu, Chen Zhu, Wei Huang, Daxing Gao, Lei Xu, Shiyuan Fang, Yunpeng Wan, Lei LiAbstract
Background:
Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by the deterioration of articular cartilage, leading to pain and joint stiffness. Ferroptosis is involved in the progression of OA and plays a pivotal role in its pathogenesis. The study aimed to investigate the mechanism by which DEAD-box helicase 6 (DDX6) regulates ferroptosis by interacting with cytoplasmic polyadenylation element-binding protein 1 (CPEB1) and contributes to OA progression by regulating osteosclerosis and microangiogenesis.
Methods:
Ferroptosis in the subchondral bone and the interaction between DDX6 and CPEB1 in OA osteoblasts were examined
Results:
Ferroptosis in OA osteoblasts, driven by mitochondrial dysfunction and the DDX6–CPEB1 interaction, was confirmed. Both DDX6 and CPEB1 were upregulated in subchondral bone of patients with OA and model mice. Upregulation or downregulation of
Conclusions:
DDX6 promotes OA progression by regulating ferroptosis through interaction with CPEB1, which in turn influences H-type microangiogenesis and osteosclerosis. Targeting DDX6 may represent a promising therapeutic strategy for OA.