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Author Spotlight: Advancing Tendon Research by Developing Mouse Assembloids to Understand Cellular Mechanisms
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Author Spotlight: Advancing Tendon Research by Developing Mouse Assembloids to Understand Cellular Mechanisms

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Tendon fibroblast inflammatory responses depend on NF-κβ and JAK/STAT signaling and alter mechanotransduction

McKenzie Sup1, MinKyu M Kim2, Lee Song2

  • 1Department of Biomedical Engineering, Columbia University, New York, NY 10027.

Biorxiv : the Preprint Server for Biology
|July 17, 2025
PubMed

Insights

Inflammation disrupts tendon healing by altering mechanosensitivity. Understanding these inflammatory pathways, including NF-κβ and JAK/STAT signaling, is crucial for developing targeted therapies to improve tendon repair outcomes.

Area of Science:

  • Biomedical Engineering
  • Musculoskeletal Biology
  • Inflammation Research

Background:

  • Tendon pathologies are common musculoskeletal injuries.
  • Inflammation plays a key role in both acute and chronic tendon healing.
  • Gaps in knowledge hinder therapeutic development for tendon healing.

Purpose of the Study:

  • Characterize the inflammatory response in tendon healing.
  • Define the roles of molecular pathways and their interaction with mechanobiology.
  • Investigate how inflammation affects tendon fibroblasts (TFs) and their response to mechanical loading.

Main Methods:

  • Developed an in vitro model simulating in vivo healing using M1 macrophage conditioned media (M1-CM) on TFs.
  • Analyzed gene expression and cytokine secretion in TFs.
  • Investigated the necessity of NF-κβ and JAK/STAT signaling pathways.
  • Assessed TF responses to mechanical loading in the presence of inflammation.
  • Utilized mathematical modeling to analyze mechanosensitivity.

Main Results:

  • M1-CM induced a robust inflammatory response in TFs, upregulating over 500 genes and increasing cytokine secretion.
  • NF-κβ and JAK/STAT pathways were essential for TF response to M1-CM.
  • Inflammation altered TF responses to mechanical loading, affecting extracellular matrix organization and G protein signaling.
  • Mathematical modeling indicated time-dependent suppression of mechanosensitivity.

Conclusions:

  • Inflammation disrupts mechanosensitivity during tendon healing.
  • NF-κβ and JAK/STAT pathways are critical mediators of inflammation in TFs.
  • Therapeutic timing of anti-inflammatory interventions may modulate rehabilitation outcomes by restoring mechanical responsiveness.
Keywords:
JAK/STATNF-κβinflammationmacrophagesmechanotransductiontendinopathy

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