The effect of local sympatholysis on bone-tendon interface healing in a murine rotator cuff repair model

Tingmo Huang; Liyang Wan; Yang Chen; Yinghong Xiong; Feifei Yuan; Shanshan Xie; Jianjun Huang; Hongbin Lu

Journal of Orthopaedic Translation (May 2023)

The effect of local sympatholysis on bone-tendon interface healing in a murine rotator cuff repair model

Tingmo Huang,
Liyang Wan,
Yang Chen,
Yinghong Xiong,
Feifei Yuan,
Shanshan Xie,
Jianjun Huang,
Hongbin Lu

Affiliations

Tingmo Huang: Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
Liyang Wan: Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
Yang Chen: Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
Yinghong Xiong: Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
Feifei Yuan: Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China; Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, China
Shanshan Xie: Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
Jianjun Huang: Department of Orthopaedics, Ningde Affiliated Hospital, Fujian Medical University, Ningde, 352000, China; Corresponding author. Ningde City Hospital, Fujian Medical University, Ningde, 352000, China.
Hongbin Lu: Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China; Corresponding author. Xiangya Hospital, No. 87, Xiangya Road, Kaifu District, Changsha, 410008, China.

Journal volume & issue: Vol. 40
pp. 1 – 12

Abstract

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Background: Although 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. Methods: Specifically, 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. Results: Immunofluorescence, 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), compared to the control group. Conclusion: The 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.

Published in Journal of Orthopaedic Translation

ISSN: 2214-031X (Print); 2214-0328 (Online)
Publisher: Elsevier
Country of publisher: Hong Kong
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the musculoskeletal system
Website: http://www.journals.elsevier.com/journal-of-orthopaedic-translation/

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