Postoperative Tendon Loading With Treadmill Running Delays Tendon‐to‐Bone Healing: Immunohistochemical Evaluation in a Murine Rotator Cuff Repair Model

Wada, Satoshi; Lebaschi, Amir; Nakagawa, Yusuke; Carballo, Camila; Uppstrom, Tyler J.; Cong, Guang‐Ting; Album, Zoe; Hall, A. N.; Liang, Ying; Deng, Xiang‐Hua; Rodeo, Scott A.

doi:10.1002/jor.24300

Cited by 26 publications

(43 citation statements)

References 36 publications

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“…M2 microscope (Zeiss, Solms, Germany) equipped with an Apotome.2 System. To quantitate the positive signals of NPY, CGRP, and SP, a region of interest (ROI) was defined at the SST attachment site according to a previous similar study 27 . The integrated optical density (OD) of positive areas were measured by the Image J software (Image J, National Institutes of Health, Bethesda, MD).…”

Section: Methodsmentioning

confidence: 99%

Treadmill exercise facilitated rotator cuff healing is coupled with regulating periphery neuropeptides expression in a murine model

Zhang

Chen

et al. 2020

Journal Orthopaedic Research

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Postoperative exercise has been found able to accelerate bone‐tendon (B‐T) healing. In this study, we systematically compared tendon‐to‐bone healing in mice subjected to postoperative treadmill exercise and free cage recovery in a murine rotator cuff repair model. Specifically, C57BL/6 mice underwent unilateral supraspinatus tendon (SST) detachment and repair were randomly allocated into treadmill group and control group. Treadmill group received daily treadmill running initiated from postoperative day 7 while the control group was allowed free cage activity. Mice were euthanized at postoperative 4 and 8 weeks for synchrotron radiation micro‐computed tomography (SR‐μCT), histology and biomechanical tests to investigate the effect of treadmill running on B‐T healing. The results indicated that treadmill running initiated at day 7 postoperatively was able to accelerate B‐T healing, as evidenced by better tendon‐to‐bone maturation and increased mechanical property. Recent studies show that peripheral neuropeptides are closely associated with musculoskeletal tissue repair. We furtherly conducted quantitative reverse transcription‐polymerase chain reaction and immunofluorescence staining to investigate the temporal‐spatial expression of calcitonin gene‐related peptide (CGRP), substance P (SP), and peripheral neuropeptide Y (NPY) to verify whether they are related to rotator cuff healing. Our results show increased expression of CGRP, SP, and NPY at the healing site under the effect of mechanical stimulation. In conclusion, delayed postoperative exercise with moderate strength appears to accelerate the early phase of B‐T healing, a process that may prove to be linked to increased expression of periphery neuropeptides known to play a role in tissue healing.

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Section: Methodsmentioning

confidence: 99%

Treadmill exercise facilitated rotator cuff healing is coupled with regulating periphery neuropeptides expression in a murine model

Zhang

Chen

et al. 2020

Journal Orthopaedic Research

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“…Mice were anesthetized with 2% isoflurane, and a bilateral, full‐thickness supraspinatus and infraspinatus tenectomy and denervation was performed . A deltoid‐splitting transacromial approach exposed the supraspinatus and infraspinatus tendons, which were then finely detached from their humeral footprint.…”

Section: Methodsmentioning

confidence: 99%

“…Mice were anesthetized with 2% isoflurane, and a bilateral, full-thickness supraspinatus and infraspinatus tenectomy and denervation was performed. 20,21 A deltoid-splitting transacromial approach exposed the supraspinatus and infraspinatus tendons, which were then finely detached from their humeral footprint. The tendons were also transected just distal to the myotendinous junction, allowing for removal of the tendon and to prevent spontaneous reattachment of the tendon to the surrounding fascia.…”

Section: Surgical Modelmentioning

confidence: 99%

The MRL/MpJ Mouse Strain Is Not Protected From Muscle Atrophy and Weakness After Rotator Cuff Tear

Talarek

Piacentini

Konja

et al. 2019

Journal Orthopaedic Research

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Chronic rotator cuff tears are a common source of shoulder pain and disability. Patients with rotator cuff tears often have substantial weakness, fibrosis, and fat accumulation, which limit successful surgical repair and postoperative rehabilitation. The Murphy Roths Large (MRL) strain of mice have demonstrated superior healing and protection against pathological changes in several disease and injury conditions. We tested the hypothesis that, compared with the commonly used C57Bl/6 (B6) strain, MRL mice would have less muscle fiber atrophy and fat accumulation, and be protected against the loss in force production that occurs after cuff tear. Adult male B6 and MRL mice were subjected to a rotator cuff tear, and changes in muscle fiber contractility and histology were measured. RNA sequencing and shotgun metabolomics and lipidomics were also performed. The muscles were harvested one month after tear. B6 and MRL mice had a 40% reduction in relative muscle force production after rotator cuff tear. RNA sequencing identified an increase in fibrosis‐associated genes and a reduction in mitochondrial metabolism genes. The markers of glycolytic metabolism increased in B6 mice, while MRL mice appeared to increase amino acid metabolism after tear. There was an accumulation of lipid after injury, although there was a divergent response between B6 and MRL mice in the types of lipid species that accrued. There were strain‐specific differences between the transcriptome, metabolome, and lipidome of B6 and MRL mice, but these differences did not protect MRL mice from weakness and pathological changes after rotator cuff tear. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:811‐822, 2020

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“…All the images were observed and captured with using a Zeiss Axio Imager (Zeiss, Solms, Germany). To quantitate the positive signals of SOX 9, a region of interest (ROI) was de ned at the SST attachment site according to aprevious similar study [19]. The SOX 9 positive cells areas were counted for three times, and the mean number per square millimeter for each sample was reported.…”

Section: Immuno Orescence Analysismentioning

confidence: 99%

Recombinant Human Bone Morphogenetic Proteins-4 Enhanced the Tendon-to-bone Attachment Healing in a Murine Model of Rotator Cuff Tear: A Randomized Controlled Trial

Chen¹,

Wang²,

Zhou³

et al. 2020

Preprint

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Background: Injuries on tendon-to-bone attachment (TBA) are common clinical dilemmas. Bone Morphogenetic Proteins-4 (BMP-4) has been found the potency in chondrogenesis. But there is rare studies focusing the influence of BMP-4 on the TBA healing. Thus, the objective of this study was to explore the effect of BMP-4 on the healing of TBA in murine model of rotator cuff tear.Methods: 120 mature C57BL/6 mice (12 weeks old) were randomly divided into BMP-4 group, noggin (an inhibitor of all BMP activities) group and control group after being established an injury model of supraspinatus tendon insertion. At week 2 and 4 after surgery, the supraspinatus tendon- humerus complex (SSTHC) were harvested for microradiographic, histologic, immunofluorescent and biomechanical evaluations.Results: Radiographic data showed that BMP-4 was able to improve the quality of subchondral bone, manifested as higher BV/TV, Tb.N, TB.Th, and lower Tb.Sp. Histologically, the BMP-4 group at week-2 and -4 showed better BTA healing interface, characterized by better organizational integration and remodeling, thicker fibrocartilage layer and more fibrocartilage cells. Immunoflorescence evaluation demonstrated the number of SOX 9 positive cells in the BMP-4 group was significantly more than that in the control or noggin group at postoperative weeks 2 and 4 (p<0.05 for all). Mechanical testing results demonstrated the failure load and stiffness in the BMP-4 group were significantly higher (p<0.05 for both), while in the noggin group were lower (p<0.05 for both), compared to the control group at postoperative weeks 4.Conclusion: BMP-4 might enhance the TBA healing by promoting the regeneration of fibrocartilaginous enthesis and mineralization, while noggin inhibited this process.Clinical Relevance: BMP-4 may be a potential therapy to augment TBA healing, and finally lead to more rapid rehabilitation and reduce risk of recurrent repair.

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Postoperative Tendon Loading With Treadmill Running Delays Tendon‐to‐Bone Healing: Immunohistochemical Evaluation in a Murine Rotator Cuff Repair Model

Cited by 26 publications

References 36 publications

Treadmill exercise facilitated rotator cuff healing is coupled with regulating periphery neuropeptides expression in a murine model

Treadmill exercise facilitated rotator cuff healing is coupled with regulating periphery neuropeptides expression in a murine model

The MRL/MpJ Mouse Strain Is Not Protected From Muscle Atrophy and Weakness After Rotator Cuff Tear

Recombinant Human Bone Morphogenetic Proteins-4 Enhanced the Tendon-to-bone Attachment Healing in a Murine Model of Rotator Cuff Tear: A Randomized Controlled Trial

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