A novel and efficient murine model for investigating tendon-to-bone healing

Abstract Background Tendon-to-bone healing is a critical challenge in sports medicine, with its cellular and molecular mechanisms yet to be explored. An efficient murine model could significantly advance our understanding of this process. However, most existing murine animal models face limitations,...

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Main Authors: Baoyun Xu, Yunjiao Wang, Gang He, Kang-lai Tang, Lin Guo, Wan Chen
Format: Article
Language:English
Published: BMC 2024-01-01
Series:Journal of Orthopaedic Surgery and Research
Subjects:
Online Access:https://doi.org/10.1186/s13018-023-04496-9
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author Baoyun Xu
Yunjiao Wang
Gang He
Kang-lai Tang
Lin Guo
Wan Chen
author_facet Baoyun Xu
Yunjiao Wang
Gang He
Kang-lai Tang
Lin Guo
Wan Chen
author_sort Baoyun Xu
collection DOAJ
description Abstract Background Tendon-to-bone healing is a critical challenge in sports medicine, with its cellular and molecular mechanisms yet to be explored. An efficient murine model could significantly advance our understanding of this process. However, most existing murine animal models face limitations, including a propensity for bleeding, restricted operational space, and a steep learning curve. Thus, the need for a novel and efficient murine animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing is becoming increasingly evident. Methods In our study, forty-four 9-week-old male C57/BL6 mice underwent transection and reattachment of the Achilles tendon insertion to investigate tendon-to-bone healing. At 2 and 4 weeks postoperatively, mice were killed for histological, Micro-CT, biomechanical, and real-time polymerase chain reaction tests. Results Histological staining revealed that the original tissue structure was disrupted and replaced by a fibrovascular scar. Although glycosaminoglycan deposition was present in the cartilage area, the native structure had been destroyed. Biomechanical tests showed that the failure force constituted approximately 44.2% and 77.5% of that in intact tissues, and the ultimate tensile strength increased from 2 to 4 weeks postoperatively. Micro-CT imaging demonstrated a gradual healing process in the bone tunnel from 2 to 4 weeks postoperatively. The expression levels of ACAN, SOX9, Collagen I, and MMPs were detected, with all genes being overexpressed compared to the control group and maintaining high levels at 2 and 4 weeks postoperatively. Conclusions Our results demonstrate that the healing process in our model is aligned with the natural healing process, suggesting the potential for creating a new, efficient, and reproducible mouse animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing. Graphical abstract
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spelling doaj.art-ebaf46b67cce45c3b99a69356815cdbd2024-03-05T16:36:20ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2024-01-0119111010.1186/s13018-023-04496-9A novel and efficient murine model for investigating tendon-to-bone healingBaoyun Xu0Yunjiao Wang1Gang He2Kang-lai Tang3Lin Guo4Wan Chen5Department of Orthopaedic Surgery/Sports Medicine Center, Southwest Hospital, Army Medical UniversityDepartment of Orthopaedic Surgery/Sports Medicine Center, Southwest Hospital, Army Medical UniversityDepartment of Orthopaedic Surgery/Sports Medicine Center, Southwest Hospital, Army Medical UniversityDepartment of Orthopaedic Surgery/Sports Medicine Center, Southwest Hospital, Army Medical UniversityDepartment of Orthopaedic Surgery/Sports Medicine Center, Southwest Hospital, Army Medical UniversityDepartment of Orthopaedic Surgery/Sports Medicine Center, Southwest Hospital, Army Medical UniversityAbstract Background Tendon-to-bone healing is a critical challenge in sports medicine, with its cellular and molecular mechanisms yet to be explored. An efficient murine model could significantly advance our understanding of this process. However, most existing murine animal models face limitations, including a propensity for bleeding, restricted operational space, and a steep learning curve. Thus, the need for a novel and efficient murine animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing is becoming increasingly evident. Methods In our study, forty-four 9-week-old male C57/BL6 mice underwent transection and reattachment of the Achilles tendon insertion to investigate tendon-to-bone healing. At 2 and 4 weeks postoperatively, mice were killed for histological, Micro-CT, biomechanical, and real-time polymerase chain reaction tests. Results Histological staining revealed that the original tissue structure was disrupted and replaced by a fibrovascular scar. Although glycosaminoglycan deposition was present in the cartilage area, the native structure had been destroyed. Biomechanical tests showed that the failure force constituted approximately 44.2% and 77.5% of that in intact tissues, and the ultimate tensile strength increased from 2 to 4 weeks postoperatively. Micro-CT imaging demonstrated a gradual healing process in the bone tunnel from 2 to 4 weeks postoperatively. The expression levels of ACAN, SOX9, Collagen I, and MMPs were detected, with all genes being overexpressed compared to the control group and maintaining high levels at 2 and 4 weeks postoperatively. Conclusions Our results demonstrate that the healing process in our model is aligned with the natural healing process, suggesting the potential for creating a new, efficient, and reproducible mouse animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing. Graphical abstracthttps://doi.org/10.1186/s13018-023-04496-9Tendon-to-bone healingMouse animal modelThe Achilles tendonEnthesis
spellingShingle Baoyun Xu
Yunjiao Wang
Gang He
Kang-lai Tang
Lin Guo
Wan Chen
A novel and efficient murine model for investigating tendon-to-bone healing
Journal of Orthopaedic Surgery and Research
Tendon-to-bone healing
Mouse animal model
The Achilles tendon
Enthesis
title A novel and efficient murine model for investigating tendon-to-bone healing
title_full A novel and efficient murine model for investigating tendon-to-bone healing
title_fullStr A novel and efficient murine model for investigating tendon-to-bone healing
title_full_unstemmed A novel and efficient murine model for investigating tendon-to-bone healing
title_short A novel and efficient murine model for investigating tendon-to-bone healing
title_sort novel and efficient murine model for investigating tendon to bone healing
topic Tendon-to-bone healing
Mouse animal model
The Achilles tendon
Enthesis
url https://doi.org/10.1186/s13018-023-04496-9
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