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IL-34 Aggravates Steroid-Induced Osteonecrosis of the Femoral Head via Promoting Osteoclast Differentiation

  • Feng Wang (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) ;
  • Hong Sung Min (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) ;
  • Haojie Shan (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) ;
  • Fuli Yin (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) ;
  • Chaolai Jiang (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) ;
  • Yang Zong (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) ;
  • Xin Ma (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) ;
  • Yiwei Lin (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) ;
  • Zubin Zhou (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital) ;
  • Xiaowei Yu (Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital)
  • Received : 2021.12.07
  • Accepted : 2022.02.23
  • Published : 2022.06.30
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Abstract

IL-34 can promote osteoclast differentiation and activation, which may contribute to steroid-induced osteonecrosis of the femoral head (ONFH). Animal model was constructed in both BALB/c and IL-34 deficient mice to detect the relative expression of inflammation cytokines. Micro-CT was utilized to reveal the internal structure. In vitro differentiated osteoclast was induced by culturing bone marrow-derived macrophages with IL-34 conditioned medium or M-CSF. The relative expression of pro-inflammation cytokines, osteoclast marker genes, and relevant pathways molecules was detected with quantitative real-time RT-PCR, ELISA, and Western blot. Up-regulated IL-34 expression could be detected in the serum of ONFH patients and femoral heads of ONFH mice. IL-34 deficient mice showed the resistance to ONFH induction with the up-regulated trabecular number, trabecular thickness, bone value fraction, and down-regulated trabecular separation. On the other hand, inflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-12, IL-2, and IL-17A, showed diminished expression in IL-34 deficient ONFH induced mice. IL-34 alone or works in coordination with M-CSF to promote osteoclastogenesis and activate ERK, STAT3, and non-canonical NF-κB pathways. These data demonstrate that IL-34 can promote the differentiation of osteoclast through ERK, STAT3, and non-canonical NF-κB pathways to aggravate steroid-induced ONFH, and IL-34 can be considered as a treatment target.

Keywords

Acknowledgement

This work was funded by the National Natural Science Foundation of China (81873993); the Clinical Science and Technology Innovation Project of Shanghai Hospital Development Center (SHDC12019X24), and the Shanghai Pudong New Area Science and Technology Development Fund (PKJ2019-Y02).

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