Dynamics of early signalling events during fracture healing and potential serum biomarkers of fracture non-union in humans

Agata N. Burska, Peter V. Giannoudis, Boon Hiang Tan, Dragos Ilas, Elena Jones, Frederique Ponchel

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

To characterise the dynamic of events during the early phases of fracture repair in humans, we investigated molecular events using gene expression profiling of bone fragments from the fracture site at different time points after trauma and immune/stromal cells recruitment at the fracture site using flow cytometry. Bone and inflammatory markers were expressed at low levels at homeostasis, while transcripts for bone constituent proteins were consistently detected at higher levels. Early after fracture (range 2–4 days), increased expression of CXCL12, suggested recruitment of immune cells associated with a change in the balance of degradation enzymes and their inhibitors. At intermediate time after fracture (4–8 days), we observed high expression of inflammatory cytokines (IL1-beta, IL6), CCL2, the T-cell activation marker CD69. Late after fracture (8–14 days), high expression of factors co-operating towards the regulation of bone turnover was detected. We identified potential soluble factors and explored circulating levels in patients for whom a union/non-union (U/NU) outcome was known. This showed a clear difference for PlGF (p = 0.003) at day 1. These findings can inform future studies further investigating the cascade of molecular events following fractures and for the prediction of fracture non-union.

Original languageEnglish
Article number492
JournalJournal of Clinical Medicine
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Fracture healing
  • Inflammation
  • Signalling

ASJC Scopus subject areas

  • General Medicine

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