Pentraxin 3 ameliorates glucocorticoid-induced osteonecrosis of the femoral head via TLR4/NF-κB/FGF21 signaling axis
Year: 2025
Type: article
Abstract: 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.
Source: Communications Biology
Authors: 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
Institutions: Shandong University, Qilu Hospital of Shandong University, Chinese Academy of Medical Sciences & Peking Union Medical College, Cancer Hospital of Chinese Academy of Medical Sciences, Capital Medical University, Beijing Jishuitan Hospital, Qingdao University, Affiliated Hospital of Qingdao University, Peking Union Medical College Hospital
Language: English
Topic: Bone and Joint Diseases
Subfield: Orthopedics and Sports Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
OpenAlex ID: W4416912089