2. Academic Validation
  3. Macrophage-derived amphiregulin induces myofibroblast transition in adipogenic lineage precursors near Staphylococcus aureus abscess in bone marrow

Macrophage-derived amphiregulin induces myofibroblast transition in adipogenic lineage precursors near Staphylococcus aureus abscess in bone marrow

  • Nat Commun. 2025 Sep 25;16(1):8409. doi: 10.1038/s41467-025-63551-7.
Bingsheng Yang # 1 2 3,  Jianwen Su # 1 2,  Jichang Wu # 1 2,  Zhongwen Wang 1 2,  Jin Hu 1 2,  Mankai Yang 1 2,  Yihuang Lin 1 2,  Mingchao Jin 1 2,  Xiaochun Bai 4,  Bin Yu 1 2,  Xianrong Zhang 5 6
Affiliations

Affiliations

  • 1 Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 2 Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 3 Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 4 Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
  • 5 Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. xianrongzh@smu.edu.cn.
  • 6 Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. xianrongzh@smu.edu.cn.
  • # Contributed equally.
PMID: 40998791 DOI: 10.1038/s41467-025-63551-7
Abstract

The formation of Staphylococcus aureus (S. aureus) abscesses is a well-established determinant of persistent skeletal infections, yet the mechanisms underlying Bacterial persistence remain elusive. Here, we demonstrate that bone marrow adiponectin-positive (Adipoq+) precursors are mobilized to surround S. aureus abscesses and undergo myofibroblast differentiation. This phenotypic transition induces vascular constriction, thereby impairing local perfusion and impeding effective Bacterial clearance. Mechanistically, macrophage-derived Amphiregulin (AREG) activates EGFR signaling on Adipoq+ cells, triggering the mTOR/YAP pathway to drive their myofibroblast transition. Importantly, genetic ablation of Adipoq+ cells, cell-specific deletion of the AREG/EGFR axis, or pharmacological inhibition of EGFR/mTOR signaling effectively alleviates fibrosis, restores vascular perfusion and Antibiotic delivery, and promotes Bacterial eradication from abscesses. Our findings implicate a macrophage-Adipoq+ cell regulatory axis that sustains S. aureus persistence in osteomyelitis and identify therapeutic targeting of this axis as a strategy to enhance Antibiotic efficacy against S. aureus skeletal infections.

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