Unraveling the link: locomotor activity exerts a dual role in predicting Achilles tendon healing and boosting regeneration in mice

IntroductionTendon disorders present significant challenges in the realm of musculoskeletal diseases, affecting locomotor activity and causing pain. Current treatments often fall short of achieving complete functional recovery of the tendon. It is crucial to explore, in preclinical research, the pat...

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Main Authors: Melisa Faydaver, Mohammad El Khatib, Valentina Russo, Mara Rigamonti, Marcello Raspa, Oriana Di Giacinto, Paolo Berardinelli, Annunziata Mauro, Ferdinando Scavizzi, Fabrizio Bonaventura, Valentina Mastrorilli, Luca Valbonetti, Barbara Barboni
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-12-01
Series:Frontiers in Veterinary Science
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Online Access:https://www.frontiersin.org/articles/10.3389/fvets.2023.1281040/full
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author Melisa Faydaver
Mohammad El Khatib
Valentina Russo
Mara Rigamonti
Marcello Raspa
Oriana Di Giacinto
Paolo Berardinelli
Annunziata Mauro
Ferdinando Scavizzi
Fabrizio Bonaventura
Valentina Mastrorilli
Luca Valbonetti
Barbara Barboni
author_facet Melisa Faydaver
Mohammad El Khatib
Valentina Russo
Mara Rigamonti
Marcello Raspa
Oriana Di Giacinto
Paolo Berardinelli
Annunziata Mauro
Ferdinando Scavizzi
Fabrizio Bonaventura
Valentina Mastrorilli
Luca Valbonetti
Barbara Barboni
author_sort Melisa Faydaver
collection DOAJ
description IntroductionTendon disorders present significant challenges in the realm of musculoskeletal diseases, affecting locomotor activity and causing pain. Current treatments often fall short of achieving complete functional recovery of the tendon. It is crucial to explore, in preclinical research, the pathways governing the loss of tissue homeostasis and its regeneration. In this context, this study aimed to establish a correlation between the unbiased locomotor activity pattern of CRL:CD1 (ICR) mice exposed to uni- or bilateral Achilles tendon (AT) experimental injuries and the key histomorphometric parameters that influence tissue microarchitecture recovery.MethodsThe study involved the phenotyping of spontaneous and voluntary locomotor activity patterns in male mice using digital ventilated cages (DVC®) with access to running wheels either granted or blocked. The mice underwent non-intrusive 24/7 long-term activity monitoring for the entire study period. This period included 7 days of pre-injury habituation followed by 28 days post-injury.Results and discussionThe results revealed significant variations in activity levels based on the type of tendon injury and access to running wheels. Notably, mice with bilateral lesions and unrestricted wheel access exhibited significantly higher activity after surgery. Extracellular matrix (ECM) remodeling, including COL1 deposition and organization, blood vessel remodeling, and metaplasia, as well as cytological tendon parameters, such as cell alignment and angle deviation were enhanced in surgical (bilateral lesion) and husbandry (free access to wheels) groups. Interestingly, correlation matrix analysis uncovered a strong relationship between locomotion and microarchitecture recovery (cell alignment and angle deviation) during tendon healing. Overall, this study highlights the potential of using mice activity metrics obtained from a home-cage monitoring system to predict tendon microarchitecture recovery at both cellular and ECM levels. This provides a scalable experimental setup to address the challenging topic of tendon regeneration using innovative and animal welfare-compliant strategies.
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spelling doaj.art-37947c53c2ae4eed964462e810874cf42023-12-21T04:18:57ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692023-12-011010.3389/fvets.2023.12810401281040Unraveling the link: locomotor activity exerts a dual role in predicting Achilles tendon healing and boosting regeneration in miceMelisa Faydaver0Mohammad El Khatib1Valentina Russo2Mara Rigamonti3Marcello Raspa4Oriana Di Giacinto5Paolo Berardinelli6Annunziata Mauro7Ferdinando Scavizzi8Fabrizio Bonaventura9Valentina Mastrorilli10Luca Valbonetti11Barbara Barboni12Unit of Basic and Applied Biosciences, Department of Biosciences, Agro-Food and Environmental Technologies, University of Teramo, Teramo, ItalyUnit of Basic and Applied Biosciences, Department of Biosciences, Agro-Food and Environmental Technologies, University of Teramo, Teramo, ItalyUnit of Basic and Applied Biosciences, Department of Biosciences, Agro-Food and Environmental Technologies, University of Teramo, Teramo, ItalyTecniplast S.p.A., Buguggiate, ItalyNational Research Council, Institute of Biochemistry and Cell Biology (CNR-IBBC/EMMA/Infrafrontier/IMPC), International Campus ‘A. Buzzati-Traverso’, Rome, ItalyUnit of Basic and Applied Biosciences, Department of Biosciences, Agro-Food and Environmental Technologies, University of Teramo, Teramo, ItalyUnit of Basic and Applied Biosciences, Department of Biosciences, Agro-Food and Environmental Technologies, University of Teramo, Teramo, ItalyUnit of Basic and Applied Biosciences, Department of Biosciences, Agro-Food and Environmental Technologies, University of Teramo, Teramo, ItalyNational Research Council, Institute of Biochemistry and Cell Biology (CNR-IBBC/EMMA/Infrafrontier/IMPC), International Campus ‘A. Buzzati-Traverso’, Rome, ItalyNational Research Council, Institute of Biochemistry and Cell Biology (CNR-IBBC/EMMA/Infrafrontier/IMPC), International Campus ‘A. Buzzati-Traverso’, Rome, ItalyPLAISANT S.r.l., Rome, ItalyUnit of Basic and Applied Biosciences, Department of Biosciences, Agro-Food and Environmental Technologies, University of Teramo, Teramo, ItalyUnit of Basic and Applied Biosciences, Department of Biosciences, Agro-Food and Environmental Technologies, University of Teramo, Teramo, ItalyIntroductionTendon disorders present significant challenges in the realm of musculoskeletal diseases, affecting locomotor activity and causing pain. Current treatments often fall short of achieving complete functional recovery of the tendon. It is crucial to explore, in preclinical research, the pathways governing the loss of tissue homeostasis and its regeneration. In this context, this study aimed to establish a correlation between the unbiased locomotor activity pattern of CRL:CD1 (ICR) mice exposed to uni- or bilateral Achilles tendon (AT) experimental injuries and the key histomorphometric parameters that influence tissue microarchitecture recovery.MethodsThe study involved the phenotyping of spontaneous and voluntary locomotor activity patterns in male mice using digital ventilated cages (DVC®) with access to running wheels either granted or blocked. The mice underwent non-intrusive 24/7 long-term activity monitoring for the entire study period. This period included 7 days of pre-injury habituation followed by 28 days post-injury.Results and discussionThe results revealed significant variations in activity levels based on the type of tendon injury and access to running wheels. Notably, mice with bilateral lesions and unrestricted wheel access exhibited significantly higher activity after surgery. Extracellular matrix (ECM) remodeling, including COL1 deposition and organization, blood vessel remodeling, and metaplasia, as well as cytological tendon parameters, such as cell alignment and angle deviation were enhanced in surgical (bilateral lesion) and husbandry (free access to wheels) groups. Interestingly, correlation matrix analysis uncovered a strong relationship between locomotion and microarchitecture recovery (cell alignment and angle deviation) during tendon healing. Overall, this study highlights the potential of using mice activity metrics obtained from a home-cage monitoring system to predict tendon microarchitecture recovery at both cellular and ECM levels. This provides a scalable experimental setup to address the challenging topic of tendon regeneration using innovative and animal welfare-compliant strategies.https://www.frontiersin.org/articles/10.3389/fvets.2023.1281040/fullAchilles tendonlocomotor activityhistomorphologyextracellular matrixhome-cage monitoringtendon regeneration
spellingShingle Melisa Faydaver
Mohammad El Khatib
Valentina Russo
Mara Rigamonti
Marcello Raspa
Oriana Di Giacinto
Paolo Berardinelli
Annunziata Mauro
Ferdinando Scavizzi
Fabrizio Bonaventura
Valentina Mastrorilli
Luca Valbonetti
Barbara Barboni
Unraveling the link: locomotor activity exerts a dual role in predicting Achilles tendon healing and boosting regeneration in mice
Frontiers in Veterinary Science
Achilles tendon
locomotor activity
histomorphology
extracellular matrix
home-cage monitoring
tendon regeneration
title Unraveling the link: locomotor activity exerts a dual role in predicting Achilles tendon healing and boosting regeneration in mice
title_full Unraveling the link: locomotor activity exerts a dual role in predicting Achilles tendon healing and boosting regeneration in mice
title_fullStr Unraveling the link: locomotor activity exerts a dual role in predicting Achilles tendon healing and boosting regeneration in mice
title_full_unstemmed Unraveling the link: locomotor activity exerts a dual role in predicting Achilles tendon healing and boosting regeneration in mice
title_short Unraveling the link: locomotor activity exerts a dual role in predicting Achilles tendon healing and boosting regeneration in mice
title_sort unraveling the link locomotor activity exerts a dual role in predicting achilles tendon healing and boosting regeneration in mice
topic Achilles tendon
locomotor activity
histomorphology
extracellular matrix
home-cage monitoring
tendon regeneration
url https://www.frontiersin.org/articles/10.3389/fvets.2023.1281040/full
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