Pentraxin 3 ameliorates glucocorticoid-induced osteonecrosis of the femoral head via TLR4/NF-κB/FGF21 signaling axis

  • Commun Biol. 2025 Dec 2;9(1):27. doi: 10.1038/s42003-025-09282-3.
Jinxu Li  #  1  2 ,  Zhonghua Zhou  #  1  2 ,  Yan Kong  3 ,  Yang Li  1 ,  Zhe Wang  1 ,  Yongkang Yang  2  4 ,  Jingyi Wang  2  4 ,  Tianyi Liu  5 ,  Xinyu Wang  6 ,  Dan Luo  7  8 ,  Fan Zhang  2  4 ,  Cheng Qiu  9  10 ,  Jingwei Liu  #  11  12  13
Affiliations
  • 1. Department of Pediatric Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, PR China.
  • 2. Cheeloo College of Medicine, Shandong University, Jinan, Shandong, PR China.
  • 3. Department of General Surgery, Muping District Traditional Chinese Medicine Hospital of Yantai City, Yantai, Shandong, PR China.
  • 4. Department of Burn and Plastic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, PR China.
  • 5. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
  • 6. Department of Anaesthesia, National Center for Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, PR China.
  • 7. Department of Oral Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, PR China.
  • 8. School of Stomatology of Qingdao University, Qingdao, Shandong, PR China.
  • 9. Department of Orthopaedic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, PR China. [email protected].
  • 10. Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, PR China. [email protected].
  • 11. Department of Pediatric Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, PR China. [email protected].
  • 12. Cheeloo College of Medicine, Shandong University, Jinan, Shandong, PR China. [email protected].
  • 13. Department of Orthopaedic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, PR China. [email protected].
  • # Contributed equally.
PMID: 41331332 DOI: 10.1038/s42003-025-09282-3
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.

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