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Pro-inflammatory activity of long noncoding RNA FOXD2-AS1 in Achilles tendinopathy
1Zhejiang Rehabilitation Medical Center, Hangzhou, 310051, Zhejiang, China.
Abstract:
Achilles tendinopathy is a prevalent clinical problem that plagues athletes and general populations. Achilles tendon healing is a complex process, and so far, there is no successful long-term solution to Achilles tendinopathy in the field of microsurgery due to its poor natural regeneration ability. Limitations in understanding the pathogenesis of Achilles tendon development and Achilles tendon injury hinder clinical treatment developments. There is an increasing demand for innovative conservative treatments that can improve Achilles tendon injury. In this study, a Sprague-Dawley rat model of Achilles tendinopathy was established. Lentiviral vectors that interfere with the expression of FOXD2-AS1, miR-21-3p, or PTEN were injected every 3 days. Rats were euthanized after 3 weeks, and the effect of FOXD2-AS1, miR-21-3p, or PTEN on Achilles tendon healing was analyzed by histological observation, biomechanical test, and examinations of inflammatory factors and tendon markers. As measured, downregulating FOXD2-AS1 or upregulating miR-21-3p improved histological structure, suppressed inflammation, promoted the expression of tendon markers, and optimized the biomechanical properties of Achilles tendon. Upregulating PTEN was capable of reversing the promoting effect of inhibition of FOXD2-AS1 on Achilles tendon healing. As concluded, deficiency of FOXD2-AS1 accelerates the healing of Achilles tendon injury and improves tendon degeneration by regulating the miR-21-3p/PTEN axis and promoting the activation of the PI3K/AKT signaling pathway.
Insights
Downregulating FOXD2-AS1 or upregulating miR-21-3p accelerates Achilles tendon healing. This pathway involves the miR-21-3p/PTEN axis and PI3K/AKT signaling, offering new therapeutic strategies for tendon injury.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Molecular Biology
Background:
- Achilles tendinopathy is a common condition with limited effective long-term treatments due to poor natural tendon regeneration.
- Understanding the molecular mechanisms of Achilles tendon injury is crucial for developing novel conservative therapies.
Purpose of the Study:
- To investigate the role of FOXD2-AS1, miR-21-3p, and PTEN in Achilles tendon healing.
- To explore the potential of targeting these molecules for therapeutic intervention in Achilles tendinopathy.
Main Methods:
- Established a Sprague-Dawley rat model of Achilles tendinopathy.
- Utilized lentiviral vectors to modulate the expression of FOXD2-AS1, miR-21-3p, and PTEN.
- Analyzed healing effects through histological, biomechanical, and molecular examinations (inflammatory factors, tendon markers).
Main Results:
- Downregulating FOXD2-AS1 or upregulating miR-21-3p significantly improved histological structure and biomechanical properties.
- These interventions suppressed inflammation and promoted tendon marker expression.
- Upregulating PTEN reversed the beneficial effects of FOXD2-AS1 inhibition.
Conclusions:
- Deficiency of FOXD2-AS1 accelerates Achilles tendon healing and improves degeneration.
- This occurs via regulation of the miR-21-3p/PTEN axis and activation of the PI3K/AKT signaling pathway.
- These findings suggest FOXD2-AS1 as a potential therapeutic target for Achilles tendon repair.
