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Peer-reviewedCC BYAdvanced science (Weinheim, Baden-Wurttemberg, Germany)

Fuyuan Huoxue Decoction Promotes Lumbar Interbody Fusion in Rats: Role of Macrophage-Driven Inflammation and the TLR9/NF-κB Pathway.

  • Hongwei Gao1
  • Han Wu1
  • Shaorong Li1
  • Weijian Wang1
  • Yijian Guo1
  • Shuai Cheng2
  • Jiayi Sun3
  • Jilong An4
  • Wei Zhang1
4 affiliations
  1. 1Department of Spinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.
  2. 2Laboratory of Sensory Neurobiology, School of Basic Medical Sciences, Hebei University, Baoding, People's Republic of China.
  3. 3School of Basic Medicine, Hebei Medical University, Shijiazhuang, People's Republic of China.
  4. 4Department of Spinal Surgery, Affiliated Hospital of Hebei University, Baoding, People's Republic of China.
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Abstract

Delayed union and pseudarthrosis remain complications of lumbar interbody fusion. We investigated Fuyuan Huoxue decoction (FY) in a rat extreme lateral interbody fusion model. FY improved bone mineral density and trabecular architecture. Reduced inflammatory macrophage infiltration and nuclear factor kappa B (NF-κB) activation at 4 weeks were accompanied by improved bony bridging at 8 weeks. Transcriptomic and network analyses nominated Toll-like receptor 9 (TLR9)/NF-κB signaling for functional investigation. FY-medicated serum reduced macrophage inflammatory markers and extracellular double-stranded DNA (dsDNA), promoted bone marrow mesenchymal stem cell (BMSC) osteogenesis, and attenuated impairment induced by inflammatory macrophage-conditioned medium. DNase treatment reduced this medium's inhibitory effects, whereas a separate exogenous dsDNA challenge impaired osteogenesis and was attenuated by a TLR9 antagonist. TLR9 agonist and antagonist experiments in BMSCs and a 2-week in vivo agonist intervention supported pathway involvement. Human nonunion single-cell data showed increased phospholipid scramblase 1 and interleukin-6 expression in myeloid cells. These findings support complementary pro-osteogenic and anti-inflammatory actions of FY and identify TLR9/NF-κB as a candidate pathway contributing to fusion repair.

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Cite

BibTeXRIS
BibTeX
@article{gao2026fuyuan,
  title = {{Fuyuan Huoxue Decoction Promotes Lumbar Interbody Fusion in Rats: Role of Macrophage-Driven Inflammation and the TLR9/NF-κB Pathway.}},
  author = {Hongwei Gao and Han Wu and Shaorong Li and Weijian Wang and Yijian Guo and Shuai Cheng and Jiayi Sun and Jilong An and Wei Zhang},
  journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
  year = {2026},
  month = oct,
  doi = {10.1002/advs.78444},
  url = {https://europepmc.org/article/MED/42958760},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Fuyuan Huoxue Decoction Promotes Lumbar Interbody Fusion in Rats: Role of Macrophage-Driven Inflammation and the TLR9/NF-κB Pathway.
AU  - Hongwei Gao
AU  - Han Wu
AU  - Shaorong Li
AU  - Weijian Wang
AU  - Yijian Guo
AU  - Shuai Cheng
AU  - Jiayi Sun
AU  - Jilong An
AU  - Wei Zhang
PY  - 2026
DA  - 2026/10/29
JO  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO  - 10.1002/advs.78444
UR  - https://europepmc.org/article/MED/42958760
AB  - Delayed union and pseudarthrosis remain complications of lumbar interbody fusion. We investigated Fuyuan Huoxue decoction (FY) in a rat extreme lateral interbody fusion model. FY improved bone mineral density and trabecular architecture. Reduced inflammatory macrophage infiltration and nuclear factor kappa B (NF-κB) activation at 4 weeks were accompanied by improved bony bridging at 8 weeks. Transcriptomic and network analyses nominated Toll-like receptor 9 (TLR9)/NF-κB signaling for functional investigation. FY-medicated serum reduced macrophage inflammatory markers and extracellular double-stranded DNA (dsDNA), promoted bone marrow mesenchymal stem cell (BMSC) osteogenesis, and attenuated impairment induced by inflammatory macrophage-conditioned medium. DNase treatment reduced this medium's inhibitory effects, whereas a separate exogenous dsDNA challenge impaired osteogenesis and was attenuated by a TLR9 antagonist. TLR9 agonist and antagonist experiments in BMSCs and a 2-week in vivo agonist intervention supported pathway involvement. Human nonunion single-cell data showed increased phospholipid scramblase 1 and interleukin-6 expression in myeloid cells. These findings support complementary pro-osteogenic and anti-inflammatory actions of FY and identify TLR9/NF-κB as a candidate pathway contributing to fusion repair.
SN  - 2198-3844
ER  -