Substance P Inhibitor Promotes Tendon Healing in a Collagenase-Induced Rat Model of Tendinopathy

Ko, Kyung Rae; Han, Soo-Hong; Choi, Sung‐Woon; An, Hyun‐Ju; Kwak, Eun-Bee; Jeong, Yunhui; Baek, Minjung; Lee, Jusung; Choi, Jun Won; Kim, Il-su; Lee, Soonchul

doi:10.1177/03635465221126175

Cited by 6 publications

(7 citation statements)

References 33 publications

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“…Second, tendon healing was evaluated for only 77 days after IRE, and there were no long-term observational results. Third, methods to quantify pain have recently been used in tendinopathy research, 9,22,43 but the accuracy of these methods requires further validation.…”

Section: Discussionmentioning

confidence: 99%

“…In the absence of hindlimb injury, rats applied equal weight on both hindlimbs, whereas an unequal distribution of weight on the hindlimbs indicated a unilateral decreased pain threshold. 22 The percentage weight borne on the right (ipsilateral) leg was determined using the following formula: (weight on right leg O weight on right leg and left leg) 3 100%. 38…”

Section: Static Weightbearingmentioning

confidence: 99%

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Irreversible Electroporation Improves Tendon Healing in a Rat Model of Collagenase-Induced Achilles Tendinopathy

Wang

Er-yang

et al. 2023

Am J Sports Med

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Background: Treatment of painful chronic tendinopathy is challenging, and there is an urgent need to develop new regenerative methods. Irreversible electroporation (IRE) can lead to localized cell ablation by electrical pulses and induce new cell and tissue growth. Previously, the authors’ group reported that electroporation-ablated tendons fully regenerated. Purpose: To assess the efficiency of IRE in improving tendon healing using a collagenase-induced Achilles tendinopathy rat model. Study Design: Controlled laboratory study. Methods: After screening for the IRE ablation parameters, a collagenase-induced Achilles tendinopathy rat model was used to assess the efficacy of IRE in improving tendon healing via biomechanical, behavioral, histological, and immunofluorescence assessments. Results: The experiments showed that the parameter of 875 V/cm 180 pulses could ablate most tenocytes, and apoptosis was the main type of death in vitro. In vivo, IRE promoted the healing process of chronic tendinopathy in the Achilles tendon of rats, based on biomechanical, behavioral, and histological assessments. Finally, immunofluorescence results revealed that IRE improved blood supply in the early stages of tendon repair and could potentially reduce neuropathic pain. Conclusion: IRE enhanced tendon tissue healing in a rat model of collagenase-induced Achilles tendinopathy. Clinical Relevance: IRE may as a potential alternative treatment for tendinopathy in clinical usage.

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Section: Discussionmentioning

confidence: 99%

Section: Static Weightbearingmentioning

confidence: 99%

Irreversible Electroporation Improves Tendon Healing in a Rat Model of Collagenase-Induced Achilles Tendinopathy

Wang

Er-yang

et al. 2023

Am J Sports Med

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“…The biomechanical test was performed as described previously. 21 Briefly, Achilles tendons were harvested from the rats at 4 and 8 weeks. Before testing, a digital caliper was used to measure the thickness, width, and length of the tendons.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of IKKβ via a DNA-Based In Situ Delivery System Improves Achilles Tendinopathy Healing in a Rat Model

Ge,

Yang,

Wei

et al. 2023

Am J Sports Med

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Background: The inhibition of IKKβ by the inhibitor 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3-pyridine carbonitrile (ACHP) is a promising strategy for the treatment of Achilles tendinopathy. However, the poor water solubility of ACHP severely hinders its in vivo application. Moreover, the effective local delivery of ACHP to the tendon and its therapeutic effects have not been reported. Purpose: To investigate the therapeutic effects of IKKβ inhibition via injection of ACHP incorporated into a DNA supramolecular hydrogel in a collagenase-induced tendinopathy rat model. Study Design: Controlled laboratory study. Methods: Dendritic DNA, a Y-shaped monomer, and a crosslinking monomer were mixed with ACHP and self-assembled into an ACHP-DNA supramolecular hydrogel (ACHP-Gel). The effects of ACHP-Gel in tendon stem/progenitor cells were investigated via RNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 120 collagenase-induced rats were randomly assigned to 5 groups: blank, phosphate-buffered saline (PBS), DNA-Gel, ACHP, and ACHP-Gel. Healing outcomes were evaluated using biomechanic and histologic evaluations at 4 and 8 weeks. Results: ACHP-Gel enhanced the solubility of ACHP and sustained its release for ≥21 days in vivo, which significantly increased the retention time of ACHP and markedly reduced the frequency of administration. RNA sequencing and qRT-PCR showed that ACHP effectively downregulated genes related to inflammation and extracellular matrix remodeling and upregulated genes related to tenogenic differentiation. The cross-sectional area ( P = .024), load to failure ( P = .002), stiffness ( P = .039), and elastic modulus ( P = .048) significantly differed between the ACHP-Gel and PBS groups at 8 weeks. The ACHP-Gel group had better histologic scores than the ACHP group at 4 ( P = .042) and 8 weeks ( P = .009). Type I collagen expression (COL-I; P = .034) and the COL-I/collagen type III ratio ( P = .015) increased while interleukin 6 expression decreased ( P < .001) in the ACHP-Gel group compared with the ACHP group at 8 weeks. Conclusion: DNA supramolecular hydrogel significantly enhanced the aqueous solubility of ACHP and increased its release-retention time. Injection frequency was markedly reduced. ACHP-Gel suppressed inflammation in Achilles tendinopathy and promoted tendon healing in a rat model. Clinical Relevance: ACHP-Gel injection is a promising strategy for the treatment of Achilles tendinopathy in clinical practice.

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“…The findings of this study showed that there was a significant difference in the mRNA levels of IL-6 between inflamed tenocytes and those that had been treated with SPI in a rat model of tendinopathy that was induced by collagenase. This provides evidence that a method such as this may have therapeutic effects on the process of tendon healing and restoration [55]. The most significant findings in this field are outlined in Table 1, which presents experimental and clinical evidence on the role of interference with IL-6 signaling as a potential preventive or therapeutic option for musculoskeletal disorders.…”

Section: Potential Role In Osteoarthritis and Tendonitismentioning

confidence: 98%

“…This was suggested in light of the fact that targeted reduction of IL-6 trans-signaling would be a more effective therapeutic approach. In a collagenase-induced rat model of tendinopathy, Ko et al (2022) investigate the therapeutic benefits of substance P inhibitor (SPI) on inflamed tenocytes. This model is used to study tendinopathy.…”

Section: Potential Role In Osteoarthritis and Tendonitismentioning

confidence: 99%

Targeting IL-6 Signaling Pathways for Musculoskeletal Disorders Treatment: Risks and Benefits

Shanshal¹,

Aljorani²,

Hussain³

2023

Al-Rafidain J Med Sci

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Pro-inflammatory mediators like IL-6 effectively mediated the majority of musculoskeletal disorders such rheumatoid arthritis (RA), osteoarthritis (OA), and tendinitis. Increased levels of IL-6 are found in the serum or synovial fluid of patients with these disorders, and these levels are correlated with the incidence and severity of the disease. IL-6 is crucial for the development of cartilage pathology, for example, by inducing a variety of pathways that are involved in the induction and spread of inflammation. The expression of anti-catabolic factors is similarly increased by IL-6, indicating a protective function. The differential impacts of IL-6 classic and trans-signaling may be the reason for this dual role of IL-6, which has so far remained poorly understood. In this article, the experimental and clinical data on the function of inhibiting IL-6 signaling in the development and progression of pathologies of the synovium, cartilage, and bones were thoroughly reviewed. By evaluating the IL-6 targeting approaches that are currently being considered in research and clinical practice, it may provide a glimpse into the future of these illnesses' treatment.

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Substance P Inhibitor Promotes Tendon Healing in a Collagenase-Induced Rat Model of Tendinopathy

Cited by 6 publications

References 33 publications

Irreversible Electroporation Improves Tendon Healing in a Rat Model of Collagenase-Induced Achilles Tendinopathy

Irreversible Electroporation Improves Tendon Healing in a Rat Model of Collagenase-Induced Achilles Tendinopathy

Inhibition of IKKβ via a DNA-Based In Situ Delivery System Improves Achilles Tendinopathy Healing in a Rat Model

Targeting IL-6 Signaling Pathways for Musculoskeletal Disorders Treatment: Risks and Benefits

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