Efferocytosis Remodels Osteoclast Metabolism and Enhances Antibacterial Defense

Abstract

Osteoclasts are metabolically specialized for bone resorption, but how apoptotic-cell uptake shapes their immune function remains unclear. During Staphylococcus aureus bone infection, osteoclasts engulfed apoptotic neutrophils. In osteoclast cultures, apoptotic-neutrophil exposure reduced multinucleation and resorption, induced host-defense programs, and enhanced antibacterial activity, whereas macrophages showed no comparable antibacterial response. MERTK was required for efficient osteoclast efferocytosis. Ctsk-Cre-mediated Mertk deletion increased bacterial burden and bone loss, whereas transplantation of MERTK-competent bone marrow restored osteoclast efferocytosis and reduced infection-associated bone damage. Transcriptomic and extracellular flux analyses revealed enhanced glycolytic activity and altered lactate handling in efferocytic osteoclasts. Lactate supplementation reduced osteoclast formation without reproducing the antibacterial phenotype. Inhibiting lactate production or export attenuated antibacterial activity in efferocytic osteoclasts, whereas blocking lactate uptake enhanced it. These findings identify osteoclast efferocytosis as an immune adaptation that links apoptotic-neutrophil clearance to metabolic remodeling and antibacterial defense in bone.

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BibTeX RIS

BibTeX

@misc{yu2026efferocytosis,
  title = {{Efferocytosis Remodels Osteoclast Metabolism and Enhances Antibacterial Defense}},
  author = {Q. Yu and J. Zhang and Y. Qu and Y. Tang and Y. Zhang and Y. Jia and Q. Dai and Z. Huang and J. Shen and N. Limjunyawong and F. Luo and C. Dou},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.13.759003},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.13.759003v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Efferocytosis Remodels Osteoclast Metabolism and Enhances Antibacterial Defense
AU  - Q. Yu
AU  - J. Zhang
AU  - Y. Qu
AU  - Y. Tang
AU  - Y. Zhang
AU  - Y. Jia
AU  - Q. Dai
AU  - Z. Huang
AU  - J. Shen
AU  - N. Limjunyawong
AU  - F. Luo
AU  - C. Dou
PY  - 2026
DA  - 2026/10/13
PB  - bioRxiv
DO  - 10.64898/2026.10.13.759003
UR  - https://www.biorxiv.org/content/10.64898/2026.10.13.759003v1
AB  - Osteoclasts are metabolically specialized for bone resorption, but how apoptotic-cell uptake shapes their immune function remains unclear. During Staphylococcus aureus bone infection, osteoclasts engulfed apoptotic neutrophils. In osteoclast cultures, apoptotic-neutrophil exposure reduced multinucleation and resorption, induced host-defense programs, and enhanced antibacterial activity, whereas macrophages showed no comparable antibacterial response. MERTK was required for efficient osteoclast efferocytosis. Ctsk-Cre-mediated Mertk deletion increased bacterial burden and bone loss, whereas transplantation of MERTK-competent bone marrow restored osteoclast efferocytosis and reduced infection-associated bone damage. Transcriptomic and extracellular flux analyses revealed enhanced glycolytic activity and altered lactate handling in efferocytic osteoclasts. Lactate supplementation reduced osteoclast formation without reproducing the antibacterial phenotype. Inhibiting lactate production or export attenuated antibacterial activity in efferocytic osteoclasts, whereas blocking lactate uptake enhanced it. These findings identify osteoclast efferocytosis as an immune adaptation that links apoptotic-neutrophil clearance to metabolic remodeling and antibacterial defense in bone.
ER  -

Abstract

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