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Axin2-lineage cells contribute to neonatal tendon regeneration
1Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, United States.
Purpose:
Tendon injuries are a challenging clinical problem with few treatment options. Identifying the molecular regulators of tendon is required for the development of new therapies. While the Wnt pathway is critical for the maintenance and differentiation of many tissues, the role of Wnt signaling in tendon cell biology remains largely unexplored.
Methods:
The effects of Wnt activation were tested in vitro using neonatal tendon-derived cells cultured in 2D and 3D conditions. The inducible Axin2CreERT2 was then used to label Axin2+ cells in vivo and cells were traced during neonatal tendon regeneration.
Results:
We showed that activation of Wnt signaling results in proliferation of neonatal tendon cells. While tendon marker expression was inhibited by Wnt activation under 2D conditions, Scx expression was not affected under 3D uniaxial tension, suggesting that the microenvironment contextualizes tendon cell response to Wnt signaling. Using an in vivo model of neonatal tendon regeneration, we further showed that Wnt signaling cells comprise a subpopulation of tenocyte and epitenon cells that proliferate after injury and are recruited during regeneration.
Discussion:
Collectively, these studies suggest that Wnt signaling may play a role in tendon cell proliferation, differentiation, and regeneration.
Insights
Wnt signaling promotes tendon cell proliferation and regeneration. Microenvironment influences Wnt signaling effects on tendon cells, suggesting therapeutic potential for tendon repair.
Area of Science:
- Biochemistry
- Cell Biology
- Regenerative Medicine
Background:
- Tendon injuries present significant clinical challenges with limited therapeutic strategies.
- Understanding molecular regulators is crucial for developing novel tendon repair therapies.
- The Wnt pathway's role in tendon cell biology is largely uncharacterized.
Purpose of the Study:
- To investigate the role of Wnt signaling in tendon cell proliferation, differentiation, and regeneration.
- To determine how the microenvironment influences tendon cell responses to Wnt activation.
Main Methods:
- In vitro studies using neonatal tendon-derived cells in 2D and 3D cultures.
- In vivo lineage tracing of Axin2-expressing cells during neonatal tendon regeneration.
- Assessment of Wnt signaling effects on cell proliferation and marker expression.
Main Results:
- Wnt signaling activation increased neonatal tendon cell proliferation.
- Tendon marker expression was inhibited by Wnt in 2D, but Scx expression was maintained in 3D under tension.
- Wnt-expressing cells were identified as a subpopulation of tenocytes and epitenon cells that proliferate and are recruited during regeneration.
Conclusions:
- Wnt signaling is implicated in tendon cell proliferation and regeneration.
- The cellular microenvironment modulates tendon cell responses to Wnt signaling.
- These findings suggest Wnt pathway modulation as a potential therapeutic approach for tendon repair.
