Tensile force impairs lip muscle regeneration under the regulation of interleukin‐10

Abstract Background Orbicularis oris muscle, the crucial muscle in speaking, facial expression and aesthetics, is considered the driving force for optimal lip repair. Impaired muscle regeneration remains the main culprit for unsatisfactory surgical outcomes. However, there is a lack of study on how...

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Main Authors: Xu Cheng, Jinfeng Dou, Jinggui Li, Yixuan Huang, Bing Shi, Jingtao Li
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Journal of Cachexia, Sarcopenia and Muscle
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Online Access:https://doi.org/10.1002/jcsm.13584
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author Xu Cheng
Jinfeng Dou
Jinggui Li
Yixuan Huang
Bing Shi
Jingtao Li
author_facet Xu Cheng
Jinfeng Dou
Jinggui Li
Yixuan Huang
Bing Shi
Jingtao Li
author_sort Xu Cheng
collection DOAJ
description Abstract Background Orbicularis oris muscle, the crucial muscle in speaking, facial expression and aesthetics, is considered the driving force for optimal lip repair. Impaired muscle regeneration remains the main culprit for unsatisfactory surgical outcomes. However, there is a lack of study on how different surgical manipulations affect lip muscle regeneration, limiting efforts to seek effective interventions. Methods In this study, we established a rat lip surgery model where the orbicularis oris muscle was injured by manipulations including dissection, transection and stretch. The effect of each technique on muscle regeneration was examined by histological analysis of myogenesis and fibrogenesis. The impact of tensile force was further investigated by the in vitro application of mechanical strain on cultured myoblasts. Transcriptome profiling of muscle satellite cells from different surgical groups was performed to figure out the key factors mediating muscle fibrosis, followed by therapeutic intervention to improve muscle regeneration after lip surgeries. Results Evaluation of lip muscle regeneration till 56 days after injury revealed that the stretch group resulted in the most severe muscle fibrosis (n = 6, fibrotic area 48.9% in the stretch group, P < 0.001, and 25.1% in the dissection group, P < 0.001). There was the lowest number of Pax7‐positive nuclei at Days 3 and 7 in the stretch group (n = 6, P < 0.001, P < 0.001), indicating impaired satellite cell expansion. Myogenesis was impaired in both the transection and stretch groups, as evidenced by the delayed peak of centrally nucleated myofibers and embryonic MyHC. Meanwhile, the stretch group had the highest percentage of Pdgfra+ fibro‐adipogenic progenitors infiltrated area at Days 3, 7 and 14 (n = 6, P = 0.003, P = 0.006, P = 0.037). Cultured rat lip muscle myoblasts exhibited impaired myotube formation and fusion capacity when exposed to a high magnitude (ε = 2688 μ strain) of mechanical strain (n = 3, P = 0.014, P = 0.023). RNA‐seq analysis of satellite cells isolated from different surgical groups demonstrated that interleukin‐10 was the key regulator in muscle fibrosis. Administration of recombinant human Wnt7a, which can inhibit the expression of interleukin‐10 in cultured satellite cells (n = 3, P = 0.041), exerted an ameliorating effect on orbicularis oris muscle fibrosis after stretching injury in surgical lip repair. Conclusions Tensile force proved to be the most detrimental manoeuvre for post‐operative lip muscle regeneration, despite its critical role in correcting lip and nose deformities. Adjunctive biotherapies to regulate the interleukin‐10‐mediated inflammatory process could facilitate lip muscle regeneration under conditions of high surgical tensile force.
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spelling doaj-art-d7064ce8cfb54e71afe86b50f6852e8a2025-08-20T01:58:56ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092024-12-011562497250810.1002/jcsm.13584Tensile force impairs lip muscle regeneration under the regulation of interleukin‐10Xu Cheng0Jinfeng Dou1Jinggui Li2Yixuan Huang3Bing Shi4Jingtao Li5State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases West China Hospital of Stomatology, Sichuan University Chengdu ChinaDepartment of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases West China Hospital of Stomatology, Sichuan University Chengdu ChinaState Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases West China Hospital of Stomatology, Sichuan University Chengdu ChinaDepartment of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases West China Hospital of Stomatology, Sichuan University Chengdu ChinaDepartment of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases West China Hospital of Stomatology, Sichuan University Chengdu ChinaDepartment of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases West China Hospital of Stomatology, Sichuan University Chengdu ChinaAbstract Background Orbicularis oris muscle, the crucial muscle in speaking, facial expression and aesthetics, is considered the driving force for optimal lip repair. Impaired muscle regeneration remains the main culprit for unsatisfactory surgical outcomes. However, there is a lack of study on how different surgical manipulations affect lip muscle regeneration, limiting efforts to seek effective interventions. Methods In this study, we established a rat lip surgery model where the orbicularis oris muscle was injured by manipulations including dissection, transection and stretch. The effect of each technique on muscle regeneration was examined by histological analysis of myogenesis and fibrogenesis. The impact of tensile force was further investigated by the in vitro application of mechanical strain on cultured myoblasts. Transcriptome profiling of muscle satellite cells from different surgical groups was performed to figure out the key factors mediating muscle fibrosis, followed by therapeutic intervention to improve muscle regeneration after lip surgeries. Results Evaluation of lip muscle regeneration till 56 days after injury revealed that the stretch group resulted in the most severe muscle fibrosis (n = 6, fibrotic area 48.9% in the stretch group, P < 0.001, and 25.1% in the dissection group, P < 0.001). There was the lowest number of Pax7‐positive nuclei at Days 3 and 7 in the stretch group (n = 6, P < 0.001, P < 0.001), indicating impaired satellite cell expansion. Myogenesis was impaired in both the transection and stretch groups, as evidenced by the delayed peak of centrally nucleated myofibers and embryonic MyHC. Meanwhile, the stretch group had the highest percentage of Pdgfra+ fibro‐adipogenic progenitors infiltrated area at Days 3, 7 and 14 (n = 6, P = 0.003, P = 0.006, P = 0.037). Cultured rat lip muscle myoblasts exhibited impaired myotube formation and fusion capacity when exposed to a high magnitude (ε = 2688 μ strain) of mechanical strain (n = 3, P = 0.014, P = 0.023). RNA‐seq analysis of satellite cells isolated from different surgical groups demonstrated that interleukin‐10 was the key regulator in muscle fibrosis. Administration of recombinant human Wnt7a, which can inhibit the expression of interleukin‐10 in cultured satellite cells (n = 3, P = 0.041), exerted an ameliorating effect on orbicularis oris muscle fibrosis after stretching injury in surgical lip repair. Conclusions Tensile force proved to be the most detrimental manoeuvre for post‐operative lip muscle regeneration, despite its critical role in correcting lip and nose deformities. Adjunctive biotherapies to regulate the interleukin‐10‐mediated inflammatory process could facilitate lip muscle regeneration under conditions of high surgical tensile force.https://doi.org/10.1002/jcsm.13584inflammation mediatorsmesenchymal stromal cellsorofacial cleftsatellite cells, skeletal musclesurgical procedures, operative
spellingShingle Xu Cheng
Jinfeng Dou
Jinggui Li
Yixuan Huang
Bing Shi
Jingtao Li
Tensile force impairs lip muscle regeneration under the regulation of interleukin‐10
Journal of Cachexia, Sarcopenia and Muscle
inflammation mediators
mesenchymal stromal cells
orofacial cleft
satellite cells, skeletal muscle
surgical procedures, operative
title Tensile force impairs lip muscle regeneration under the regulation of interleukin‐10
title_full Tensile force impairs lip muscle regeneration under the regulation of interleukin‐10
title_fullStr Tensile force impairs lip muscle regeneration under the regulation of interleukin‐10
title_full_unstemmed Tensile force impairs lip muscle regeneration under the regulation of interleukin‐10
title_short Tensile force impairs lip muscle regeneration under the regulation of interleukin‐10
title_sort tensile force impairs lip muscle regeneration under the regulation of interleukin 10
topic inflammation mediators
mesenchymal stromal cells
orofacial cleft
satellite cells, skeletal muscle
surgical procedures, operative
url https://doi.org/10.1002/jcsm.13584
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AT yixuanhuang tensileforceimpairslipmuscleregenerationundertheregulationofinterleukin10
AT bingshi tensileforceimpairslipmuscleregenerationundertheregulationofinterleukin10
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