Scholarlink

Background <p>Midfacial hypoplasia is a common craniofacial deformity. Trans-sutural distraction osteogenesis (TSDO), which applies mechanical force to stimulate bone formation at the zygomaticomaxillary sutures (ZMS), has emerged as an effective therapeutic strategy. However, the underlying mechanisms of TSDO-induced osteogenesis remain unclear, resulting in prolonged treatment durations and limited clinical application. </p> Methods <p>A TSDO model was established in 4-week-old C57BL/6 mice and neutrophil-depleted mice to investigate the role of neutrophils in bone regeneration at the ZMS. Single-cell RNA sequencing was used to characterize neutrophil dynamics and heterogeneity during TSDO, and intercellular signaling pathways were identified through CellChat analysis. Additionally, in vitro stretching experiments using differentiated HL-60 cells were performed to assess the mechanosensitive behavior of neutrophils.</p> Results <p>In the TSDO model, mechanical distraction significantly increased neutrophil infiltration in the ZMS and surrounding bone marrow. Neutrophil depletion impaired distraction-induced bone formation. Single-cell sequencing revealed that the Jun<sup>+</sup> neutrophil subset (Jun-Neu) facilitated the osteogenic differentiation of suture-derived stem cells (SuSCs) via secretion of oncostatin M (OSM). In vitro, mechanical stretching (10%, 0.5&#xa0;Hz) activated the phosphoinositide 3-kinase (PI3K)-AKT pathway in neutrophils, enhancing OSM release and promoting the osteogenic differentiation of SuSCs.</p> Conclusions <p>This study identifies a mechanical force–neutrophil–bone regeneration axis in TSDO, highlighting the critical role of Jun-Neu-derived OSM in promoting osteogenesis. These findings provide theoretical insights for optimizing TSDO-based clinical strategies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Mechanical force-induced oncostatin M secretion by Jun-positive neutrophils promotes craniofacial bone regeneration for midface hypoplasia treatment

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月1日

查看全文
  • Zhixuan Sun,
  • Yujie Chen,
  • Pengbing Ding,
  • Zheng Wang,
  • Zhiyu Lin,
  • Binyi Zhou,
  • Fengyi Hu,
  • Enhang Lu,
  • Haibo Xiang,
  • Xin Yang,
  • Peiyang Zhang,
  • Zhenmin Zhao

摘要

Background

Midfacial hypoplasia is a common craniofacial deformity. Trans-sutural distraction osteogenesis (TSDO), which applies mechanical force to stimulate bone formation at the zygomaticomaxillary sutures (ZMS), has emerged as an effective therapeutic strategy. However, the underlying mechanisms of TSDO-induced osteogenesis remain unclear, resulting in prolonged treatment durations and limited clinical application.

Methods

A TSDO model was established in 4-week-old C57BL/6 mice and neutrophil-depleted mice to investigate the role of neutrophils in bone regeneration at the ZMS. Single-cell RNA sequencing was used to characterize neutrophil dynamics and heterogeneity during TSDO, and intercellular signaling pathways were identified through CellChat analysis. Additionally, in vitro stretching experiments using differentiated HL-60 cells were performed to assess the mechanosensitive behavior of neutrophils.

Results

In the TSDO model, mechanical distraction significantly increased neutrophil infiltration in the ZMS and surrounding bone marrow. Neutrophil depletion impaired distraction-induced bone formation. Single-cell sequencing revealed that the Jun+ neutrophil subset (Jun-Neu) facilitated the osteogenic differentiation of suture-derived stem cells (SuSCs) via secretion of oncostatin M (OSM). In vitro, mechanical stretching (10%, 0.5 Hz) activated the phosphoinositide 3-kinase (PI3K)-AKT pathway in neutrophils, enhancing OSM release and promoting the osteogenic differentiation of SuSCs.

Conclusions

This study identifies a mechanical force–neutrophil–bone regeneration axis in TSDO, highlighting the critical role of Jun-Neu-derived OSM in promoting osteogenesis. These findings provide theoretical insights for optimizing TSDO-based clinical strategies.