ArticleStem cell research & therapy2021
Intramuscular injection of Botox causes tendon atrophy by induction of senescence of tendon-derived stem cells.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- iCLAP: an innovative method for integrable co-detection of low-abundance antigens with high-plex immunostaining.Nature communications · 2026Article
- Stem cell-derived exosomes: a potential therapeutic strategy for enhancing tendon stem/progenitor cells function in tendon-bone healing.Journal of orthopaedic surgery and research · 2025Review
- Cellular senescence impairs tendon extracellular matrix remodeling in response to mechanical unloading.Aging cell · 2024Article
- LeveragingFrontiers in bioengineering and biotechnology · 2024Review
- Animal model for tendinopathy.Journal of orthopaedic translation · 2023Review
- Enhanced contrast synchrotron X-ray microtomography for describing skeleton-associated soft tissue defects in zebrafish mutants.Frontiers in endocrinology · 2023Article
- Challenges and perspectives of tendon-derived cell therapy for tendinopathy: from bench to bedside.Stem cell research & therapy · 2022Review
- In Vitro 3D Mechanical Stimulation to Tendon-Derived Stem Cells by Bioreactor.Methods in molecular biology (Clifton, N.J.) · 2022Article
- A bio-inductive collagen scaffold that supports human primary tendon-derived cell growth for rotator cuff repair.Journal of orthopaedic translation · 2021Article
- Characterization of Tendon-Derived Stem Cells and Rescue Tendon Injury.Stem cell reviews and reports · 2021Review
- MicroRNA engineered umbilical cord stem cell-derived exosomes direct tendon regeneration by mTOR signaling.Journal of nanobiotechnology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBotulinum toxin (Botox) injection is in widespread clinical use for the treatment of muscle spasms and tendinopathy but the mechanism of action is poorly understood. HYPOTHESIS: We hypothesised that the reduction of patellar-tendon mechanical-loading following intra-muscular injection of Botox results in tendon atrophy that is at least in part mediated by the induction of senescence of tendon-derived stem cells (TDSCs). STUDY
designControlled laboratory study
methodsA total of 36 mice were randomly divided into 2 groups (18 Botox-injected and 18 vehicle-only control). Mice were injected into the right vastus lateralis of quadriceps muscles either with Botox (to induce mechanical stress deprivation of the patellar tendon) or with normal saline as a control. At 2 weeks post-injection, animals were euthanized prior to tissues being harvested for either evaluation of tendon morphology or in vitro studies. TDSCs were isolated by cell-sorting prior to determination of viability, differentiation capacity or the presence of senescence markers, as well as assessing their response to mechanical loading in a bioreactor. Finally, to examine the mechanism of tendon atrophy in vitro, the PTEN/AKT-mediated cell senescence pathway was evaluated in TDSCs from both groups.
resultsTwo weeks after Botox injection, patellar tendons displayed several atrophic features including tissue volume reduction, collagen fibre misalignment and increased degradation. A colony formation assay revealed a significantly reduced number of colony forming units of TDSCs in the Botox-injected group compared to controls. Multipotent differentiation capacities of TDSCs were also diminished after Botox injection. To examine if mechanically deprived TDSC are capable of forming tendon tissue, we used an isolated bioreactor system to culture tendon constructs using TDSC. These results showed that TDSCs from the Botox-treated group failed to restore tenogenic differentiation after appropriate mechanical loading. Examination of the signalling pathway revealed that injection of Botox into quadriceps muscles causes PTEN/AKT-mediated cell senescence of TDSCs.
conclusionIntramuscular injection of Botox interferes with tendon homeostasis by inducing tendon atrophy and senescence of TDSCs. Botox injection may have long-term adverse consequences for the treatment of tendinopathy. CLINICAL RELEVANCE: Intramuscular Botox injection for tendinopathy or tendon injury could result in adverse effects in human tendons and evaluation of its long-term efficacy is warranted.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.