ArticleFrontiers in aging neuroscience2015
Activation of EphA4 and EphB2 Reverse Signaling Restores the Age-Associated Reduction of Self-Renewal, Migration, and Actin Turnover in Human Tendon Stem/Progenitor Cells.
Article in Frontiers in aging neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Beyond local injury: pathogenic roles of metabolic, endocrine, and aging-associated systemic factors in tendinopathy and novel therapeutic strategies.Journal of orthopaedic surgery and research · 2026Review
- Giving It a Twist: One-Step Fabrication of Aligned Biomimetic Yarn Scaffolds via Rotational Melt Electrofibrillation.Advanced healthcare materials · 2026Article
- The current status of various preclinical therapeutic approaches for tendon repair.Annals of medicine · 2024Review
- Aged Tendons Exhibit Altered Mechanisms of Strain-Dependent Extracellular Matrix Remodeling.Journal of biomechanical engineering · 2024Article
- Inhibition of the CoREST Repressor Complex Promotes Wound Re-Epithelialization through the Regulation of Keratinocyte Migration.The Journal of investigative dermatology · 2024Article
- Role of tendon-derived stem cells in tendon and ligament repair: focus on tissue engineer.Frontiers in bioengineering and biotechnology · 2024Review
- Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression.Signal transduction and targeted therapy · 2023Article
- Effect of Aging on Tendon Biology, Biomechanics and Implications for Treatment Approaches.International journal of molecular sciences · 2023Review
- Targeting Senescent Tendon Stem/Progenitor Cells to Prevent or Treat Age-Related Tendon Disorders.Stem cell reviews and reports · 2023Review
- Impact of aging on tendon homeostasis, tendinopathy development, and impaired healing.Connective tissue research · 2023Review
- Effects of aging on the histology and biochemistry of rat tendon healing.BMC musculoskeletal disorders · 2021Article
- Characterization of Tendon-Derived Stem Cells and Rescue Tendon Injury.Stem cell reviews and reports · 2021Review
- Basic Research on Tendon Repair: Strategies, Evaluation, and Development.Frontiers in medicine · 2021Review
- Inhibition of JAK-STAT Signaling Pathway Alleviates Age-Related Phenotypes in Tendon Stem/Progenitor Cells.Frontiers in cell and developmental biology · 2021Article
- AQP1 modulates tendon stem/progenitor cells senescence during tendon aging.Cell death & disease · 2020Article
- Loss of tenomodulin expression is a risk factor for age-related intervertebral disc degeneration.Aging cell · 2020Article
- Aged Tendon Stem/Progenitor Cells Are Less Competent to Form 3D Tendon Organoids Due to Cell Autonomous and Matrix Production Deficits.Frontiers in bioengineering and biotechnology · 2020Article
- Tendon stem/progenitor cell ageing: Modulation and rejuvenation.World journal of stem cells · 2019Review
- Aspirin inhibits inflammation and scar formation in the injury tendon healing through regulating JNK/STAT-3 signalling pathway.Cell proliferation · 2019Article
- Regulatory mechanisms and clinical manifestations of musculoskeletal aging.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2019Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tendon tissues, due to their composition and function, are prone to suffer age-related degeneration and diseases as well as to respond poorly to current repair strategies. It has been suggested that local stem cells, named tendon stem/progenitor cells (TSPCs), play essential roles in tendon maintenance and healing. Recently, we have shown that TSPC exhibit a distinct age-related phenotype involving transcriptomal shift, poor self-renewal, and elevated senescence coupled with reduced cell migration and actin dynamics. Here, we report for the first time the significant downregulation of the ephrin receptors EphA4, EphB2 and B4 and ligands EFNB1 in aged-TSPC (A-TSPC). Rescue experiments, by delivery of target-specific clustered proteins, revealed that activation of EphA4- or EphB2-dependent reverse signaling could restore the migratory ability and normalize the actin turnover of A-TSPC. However, only EphA4-Fc stimulation improved A-TSPC cell proliferation to levels comparable to young-TSPC (Y-TSPC). Hence, our novel data suggests that decreased expression of ephrin receptors during tendon aging and degeneration limits the establishment of appropriate cell-cell interactions between TSPC and significantly diminished their proliferation, motility, and actin turnover. Taken together, we could propose that this mechanism might be contributing to the inferior and delayed tendon healing common for aged individuals.
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