Healing of rotator cuff tendons using botulinum toxin A and immobilization in a rat model

Gilotra, Mohit N.; Shorofsky, Michael; Stein, Jason; Murthi, Anand M.

doi:10.1186/s12891-016-0978-y

Cited by 13 publications

(8 citation statements)

References 42 publications

(43 reference statements)

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“…Several studies have reported pain relief following Botox injection after achieving sufficient suppression of muscular function in lateral epicondylitis [ 14 , 22 ]. A potential mechanism of improved tendon function was reported in an animal study where Botox was injected into the supraspinatus muscle for repair of rotator cuff injury showing an improvement of collagen fibres alignment at the tendon-bone interface [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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

Chen

Mitchell

et al. 2021

Stem Cell Res Ther

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Background Botulinum 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 design Controlled laboratory study Methods A 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. Results Two 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. Conclusion Intramuscular 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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Section: Introductionmentioning

confidence: 99%

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

Chen

Mitchell

et al. 2021

Stem Cell Res Ther

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“…Col I, essential for fibrous tissues repair and regeneration, is one the main ECM protein in tendon [19]. The collagen fibers longitudinal arrangement is important to provide mechanical properties of tendons and can maintain the physiological structure [20, 21]. The rat model showed that the control group had more Col I and Col III accumulation in the wound area.…”

Section: Discussionmentioning

confidence: 99%

Relaxin inhibits patellar tendon healing in rats: a histological and biochemical evaluation

Bai

et al. 2019

BMC Musculoskelet Disord

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Background Female patients are more likely to have tendon injuries than males, especially those who has a higher concentration of relaxin. Previous studies have demonstrated that relaxin attenuates extracellular matrix (ECM) formation. However, the mechanism of relaxin on tendon repair remains unclear. We hypothesize that relaxin inhibits tendon healing by disrupting collagen synthesis. Methods A patellar tendon window defect model was established using Sprague-Dawley rats. The center of the patellar tendon was removed from the patella distal apex and inserted to the tibia tuberosity in width of 1 mm. Then, the rats were injected with saline (0.2 μg/kg/day) or relaxin (0.2 μg/kg/day) for two and four weeks, which was followed by biomechanical analysis and histological and histochemical examination. Results Mechanical results indicated that relaxin induces a significant decrease in tear resistance, stiffness, and Young’s modulus compared to those rats without relaxin treatment. In addition, it was shown that relaxin activates relaxin family peptide receptor 1(RXFP1), disturbs the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs), and reduces the deposition of collagen in injury areas. Conclusions Relaxin impairs tendon healing in rats. Also, relaxin might lead to tendon injury more commonly for females than males. Electronic supplementary material The online version of this article (10.1186/s12891-019-2729-3) contains supplementary material, which is available to authorized users.

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“…Mechanical stability and the local mechanical environment are required for optimal repair of injured tissues for both tendon and bone [14,16,74–76]. While complete immobilization is not ideal for either tendon or bone repair [4,75,77–80], too much loading can lead to failed repair, gapping (in tendon) and non-unions (in bone) [81–84]. There exists a range of therapeutic loading that promotes tissue regeneration while allowing for sufficient healing processes [85,86].…”

Section: Intact Tendon Maintains Mechanical Stability Of Healing Bonementioning

confidence: 99%

Tendon Healing in the Context of Complex Fractures

Ganji

Killian

2018

Clinic Rev Bone Miner Metab

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Tendons connect muscle to bone and play an integral role in bone and joint alignment and loading. Tendons act as pulleys that provide anchorage of muscle forces for joint motion and stability, as well as for fracture reduction and realignment. Patients that experience complex fractures also have concomitant soft tissue injuries, such as tendon damage or rupture. Tendon injuries that occur at the time of bone fracture have long-term ramifications on musculoskeletal health, yet these injuries are often disregarded in clinical treatment and diagnosis for patients with bone fractures as well as in basic science approaches for understanding bone repair processes. Delayed assessment of soft tissue injuries during evaluation of trauma can lead to chronic pain, dysfunction, and delayed bone healing even following successful fracture repair, highlighting the importance of identifying and treating damaged tendons early. Treatment strategies for bone repair, such as mechanical stabilization and biological therapeutics, can impact tendon healing and function. Because poor tendon healing following complex fracture can significantly impact the function of tendon during bone fracture healing, a need exists to understand the healing process of complex fractures more broadly, beyond the healing of bone. In this review, we explored the mechanical and biological interaction of bone and tendon in the context of complex fracture, as well as the relevance and potential ramifications of tendon damage following bone fracture, which has particular impact on patients that experience complex fractures, such as from combat, automobile accidents, and other trauma.

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Healing of rotator cuff tendons using botulinum toxin A and immobilization in a rat model

Cited by 13 publications

References 42 publications

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

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

Relaxin inhibits patellar tendon healing in rats: a histological and biochemical evaluation

Tendon Healing in the Context of Complex Fractures

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