Dataset Information

Biomechanical, Histologic, and Molecular Evaluation of Tendon Healing in a New Murine Model of Rotator Cuff Repair.

ABSTRACT: PURPOSE:To develop a clinically relevant, robust murine model of rotator cuff tendon repair to examine cellular and molecular mechanisms of healing. METHODS:Sixty C57BL/6 male mice underwent rotator cuff transection and repair using microsurgical techniques. A modified Kessler suturing technique was used prior to tendon detachment. Sutures were passed through 2 intersecting bone tunnels that were made at the tendon attachment site. Mice were sacrificed at 2 and 4 weeks with subsequent biomechanical, histologic, micro-CT, and gene expression evaluations. RESULTS:Failure forces in the 2- and 4-week groups were 36% and 75% of the intact tendon, respectively. Histologic evaluation revealed complete reattachment of the tendon with no observable gap. Healing occurred by formation of fibrovascular tissue at the tendon-bone interface, similar to larger animal models. Molecular analysis revealed gene expression consistent with gradual healing of the reattached tendon over a period of 4 weeks. Comparisons were made using 1-way analysis of variance. CONCLUSIONS:This model is distinguished by use of microsurgical suturing techniques, which provides a robust, reproducible, and economic animal model to study various aspects of rotator cuff pathology. CLINICAL RELEVANCE:Improvement of clinical outcomes of rotator cuff pathology requires in-depth understanding of the underlying cellular and molecular mechanisms of healing. This study presents a robust murine model of supraspinatus repair to serve as a standard research tool for basic and translational investigations into signaling pathways, gene expression, and the effect of biologic augmentation approaches.

SUBMITTER: Lebaschi AH

PROVIDER: S-EPMC6340398 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Biomechanical, Histologic, and Molecular Evaluation of Tendon Healing in a New Murine Model of Rotator Cuff Repair.

Lebaschi Amir H AH Deng Xiang-Hua XH Camp Christopher L CL Zong Jianchun J Cong Guang-Ting GT Carballo Camila B CB Album Zoe Z Rodeo Scott A SA

Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association 20180216 4

<h4>Purpose</h4>To develop a clinically relevant, robust murine model of rotator cuff tendon repair to examine cellular and molecular mechanisms of healing.<h4>Methods</h4>Sixty C57BL/6 male mice underwent rotator cuff transection and repair using microsurgical techniques. A modified Kessler suturing technique was used prior to tendon detachment. Sutures were passed through 2 intersecting bone tunnels that were made at the tendon attachment site. Mice were sacrificed at 2 and 4 weeks with subseq ...[more]

PMID: 29459078

Similar Datasets

Project description:BackgroundAlthough neuroregulation plays an important role in tissue healing, the key neuroregulatory pathways and related neurotransmitters involved in bone-tendon interface (BTI) healing are still unknown. It is reported that sympathetic nerves can regulate cartilage and bone metabolism, which are the basic aspects of BTI repair after injury, through the release of norepinephrine (NE). Thus, the purpose of this study was to explore the effect of local sympatholysis (LS) on BTI healing in a murine rotator cuff repair model.MethodsSpecifically, C57BL/6 mice underwent unilateral supraspinatus tendon (SST) detachment and repair was established on a total of 174 mature C57BL/6 mice (12 weeks old): 54 mice were used to examine the sympathetic fibers and its neurotransmitter NE for the representation of sympathetic innervation of BTI, while the rest of them were randomly allocated into (LS) group and control group to verify the effect of sympathetic denervation during BTI healing. The LS group were intervened with fibrin sealant containing 10 ng/ml guanethidine, while the control group received fibrin sealant only. Mice were euthanized at postoperative 2, 4 and 8 weeks for immunofluorescent, qRT-PCR, ELISA, Micro-computed tomography (CT), histology and biomechanical evaluations.ResultsImmunofluorescence, qRT-PCR and ELISA evaluations indicated that there were the expression of tyrosine hydroxylase (TH), NE and β2-adrenergic receptor (β2-AR) at the BTI site. All the above showed a trend of increasing at the early postoperative stage and they started to decrease with the healing time after a significant peak. Meanwhile, local sympathetic denervation of BTI was achieved after the use of guanethidine as shown in the NE ELISA outcomes in two groups. QRT-PCR analysis revealed that the healing interface in the LS group expressed more transcription factors, such as Runx2, Bmp2, Sox9, and Aggrecan, than the control group. Further, radiographic data showed that the LS group significantly possessed higher bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and lower trabecular spacing (Tb.Sp) than the control group. Also, histological test results showed that there was more fibrocartilage regenerated at the healing interface in the LS group compared with the control group. Mechanical testing results demonstrated that the failure load, ultimate strength and stiffness in the LS group were significantly higher at postoperative week 4 (P < 0.05), but not at postoperative week 8 (P > 0.05), compared to the control group.ConclusionThe regulation of sympathetic innervation was involved in the healing process of injured BTI, and local sympathetic denervation by using guanethidine was beneficial for BTI healing outcomes.The translational potential of this article: This is the first study to evaluate the expression and specific role of sympathetic innervation during BTI healing. The findings of this study also imply that the antagonists of β2-AR could serve as a potential therapeutic strategy for BTI healing. Also, we firstly successfully constructed a local sympathetic denervation mouse model by using guanethidine loaded fibrin sealant, which provided a new effective methodology for future neuroskeletal biology study.

Dataset Information

Biomechanical, Histologic, and Molecular Evaluation of Tendon Healing in a New Murine Model of Rotator Cuff Repair.

Publications

Biomechanical, Histologic, and Molecular Evaluation of Tendon Healing in a New Murine Model of Rotator Cuff Repair.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets