Jinxu Li, Zhonghua Zhou, Yan Kong, Yang Li, Zhe Wang, Yongkang Yang, Jingyi Wang, Tianyi Liu, Xinyu Wang, Dan Luo, Fan Zhang, Cheng Qiu, Jingwei Liu
These findings establish the PTX3-TLR4/NF-κB-FGF21 axis as a key mechanism and suggest PTX3 supplementation as a potential therapeutic strategy against glucocorticoid-induced ONFH.
Glucocorticoid-induced osteonecrosis of the femoral head (ONFH) is a debilitating bone disorder characterized by impaired osteogenesis and apoptosis-driven bone collapse. This study identifies significantly reduced pentraxin 3 (PTX3) levels in patient samples and models. Recombinant PTX3 (rPTX3) alleviated dexamethasone-induced osteogenic suppression and apoptosis in vitro by activating TLR4/NF-κB pathway to downregulate fibroblast growth factor 21 (FGF21). In Ptx3-knockout mice, glucocorticoid-induced bone deterioration was exacerbated, while PTX3 administration preserved bone architecture. Pharmacological blockade of TLR4/NF-κB signaling abolished PTX3's protective effects. Notably, FGF21 suppression by activating transcription factor 3 (ATF3) retained bone-protective effects even in PTX3-deficient models, underscoring its role as a downstream effector. These findings establish the PTX3-TLR4/NF-κB-FGF21 axis as a key mechanism and suggest PTX3 supplementation as a potential therapeutic strategy against glucocorticoid-induced ONFH.