Intramuscular injection of Botox causes tendon atrophy by induction of senescence of tendon-derived stem cells

Abstract Background Botulinum toxin (Botox) injection is in widespread clinical use for the treatment of muscle spasms and tendinopathy but mechanism action poorly understood. Hypothesis We hypothesised that reduction patellar-tendon mechanical-loading following intra-muscular Botox results tendon atrophy at least part mediated by induction senescence tendon-derived stem cells (TDSCs). Study design Controlled laboratory study Methods A total 36 mice were randomly divided into 2 groups (18 Botox-injected 18 vehicle-only control). Mice injected right vastus lateralis quadriceps muscles either with (to induce mechanical stress deprivation patellar tendon) or normal saline as a control. At weeks post-injection, animals euthanized prior to tissues being harvested evaluation morphology vitro studies. TDSCs isolated cell-sorting determination viability, differentiation capacity presence markers, well assessing their response loading bioreactor. Finally, examine vitro, PTEN/AKT-mediated cell pathway was evaluated from both groups. Results Two after injection, tendons displayed several atrophic features including tissue volume reduction, collagen fibre misalignment increased degradation. colony formation assay revealed significantly reduced number forming units group compared controls. Multipotent capacities also diminished injection. To if mechanically deprived TDSC are capable tissue, we used an bioreactor system culture constructs using TDSC. These showed Botox-treated failed restore tenogenic appropriate loading. Examination signalling causes TDSCs. Conclusion Intramuscular interferes homeostasis inducing may have long-term adverse consequences tendinopathy. Clinical relevance injury could result effects human its efficacy warranted.