ArticleJournal of orthopaedic translation2021
Early treadmill running delays rotator cuff healing via Neuropeptide Y mediated inactivation of the Wnt/β-catenin signaling.
Article in Journal of orthopaedic translation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Sirtuins in intervertebral disc degeneration: current understanding.Molecular medicine (Cambridge, Mass.) · 2024Pooled it
- A Hypothalamic Oxytocinergic-Sympathetic Axis Couples Anxiety Dysregulation With Impaired Tendon-Bone Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Postoperative exercise modulating gut microbiota and associated metabolites to facilitate bone-tendon healing in rotator cuff tears.BMC musculoskeletal disorders · 2026Article
- From physical modalities to energy-responsive biomaterials: Current strategies and challenges in tendon-to-bone healing.Bioactive materials · 2026Review
- Targeting Caveolin-1 for enhanced rotator cuff repair: findings from single-cell RNA sequencing.Cell death discovery · 2025Article
- Single-cell sequencing reveals cellular heterogeneity and molecular mechanisms in tendon and enthesis injury repair.Frontiers in physiology · 2025Review
- Tendon mechanobiology in the context of tendon biofabrication.Frontiers in bioengineering and biotechnology · 2025Review
- Comparative effect of skeletal stem cells versus bone marrow mesenchymal stem cells on rotator cuff tendon-bone healing.Journal of orthopaedic translation · 2024Article
- Aerobic exercise training engages the canonical wnt pathway to improve pulmonary function and inflammation in COPD.BMC pulmonary medicine · 2024Article
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- The effect of local sympatholysis on bone-tendon interface healing in a murine rotator cuff repair model.Journal of orthopaedic translation · 2023Article
- Exosomes from CD133Journal of orthopaedic translation · 2023Article
- External stimulation: A potential therapeutic strategy for tendon-bone healing.Frontiers in bioengineering and biotechnology · 2023Review
- Rotator cuff healing is regulated by the lymphatic vasculature.Journal of orthopaedic translation · 2023Article
- Deconstruction of Vermal Cerebellum in Ramp Locomotion in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Mechanical stimulation improves rotator cuff tendon-bone healing via activating IL-4/JAK/STAT signaling pathway mediated macrophage M2 polarization.Journal of orthopaedic translation · 2022Article
- Intermittent fasting promotes repair of rotator cuff injury in the early postoperative period by regulating the gut microbiota.Journal of orthopaedic translation · 2022Article
- The importance of microstructure in R&D and applications of biomaterials and biological modulation in orthopaedics.Journal of orthopaedic translation · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDefining the optimal rehabilitation programs for rotator cuff healing remains a challenge. Early treadmill running may have negative effects on tendon-bone interface (TBI) healing with increased expression of Neuropeptide Y (NPY). However, the underlying mechanism is still unknown.
methodsThe mice were randomly assigned to four groups: control group, treadmill group, treadmill + BIBO3304 group and BIBO3304 group alone. Specifically, the control group was allowed free cage activity without any treatment after surgery. The treadmill group received early treadmill running initiated from postoperative day 2. The treadmill + BIBO3304 group received treadmill running combined with intra-articular injection of BIBO3304 postoperatively. The BIBO3304 group only received type 1 NPY receptor (Y1 receptor, Y1R) antagonist BIBO3304 postoperatively. Healing outcomes of the rotator cuff were evaluated by histological analysis, synchrotron radiation micro-computed tomography (SR-μCT) scanning, and biomechanical testing at 4 and 8 weeks after surgery. The expression of NPY and its Y1 receptor during the treadmill running were tested by immunofluorescence. In addition, the related signaling pathway of Neuropeptide Y among all groups was detected by immunohistochemistry and western-blot.
resultsImmunofluorescence results show that early treadmill training could lead to a significant increase in the expression of NPY at the healing site, and Y1R was widely expressed in both normal or injured rotator cuff without statistical difference. At the same time, early treadmill running delayed the healing of rotator cuff, as indicated with unsatisfactory outcomes, including a significantly lower histological score, decreased bone formation and inferior biomechanical properties at postoperative week 4 and 8. Moreover, the use of BIBO3304 could partly alleviate the negative effects of early treadmill running on the healing of rotator cuff and promote the natural healing process of rotator cuff, as evidenced by significant differences observed between the treadmill and treadmill + BIBO3304 groups, as well as observed between the control and BIBO3304 groups. On the other hand, the expressions of Wnt3a and β-catenin in the treadmill group were significantly lower compared with the other groups, while the expression in the BIBO3304 group was the highest, as evaluated by immunohistochemistry and western-blot.
conclusionsEarly treadmill running increased the expression of NPY at the RC healing site, which might burden the expression of Wnt3a/β-catenin and delay the healing process, inhibition of Y1 receptor with BIBO3304 could promote bone-tendon healing through the Wnt/β-catenin signaling.The translational potential of this article: This is the first study to evaluate the specific role of the NPY-Y1R axis and its underlying mechanism by which early treadmill running delays bone-tendon healing. Further, our study may provide references of precise and individualized exercise-based rehabilitation strategies for TBI healing in clinic. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This is the first study to evaluate the specific role of the NPY-Y1R axis and its underlying mechanism by which early treadmill running delays bone-tendon healing. Further, our study may provide references of precise and individualized exercise-based rehabilitation strategies for TBI healing in clinic.
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