Kartogenin Enhances Collagen Organization and Mechanical Strength of the Repaired Enthesis in a Murine Model of Rotator Cuff Repair

Wang, Dean; Tan, Haidong; Lebaschi, Amir; Nakagawa, Yusuke; Wada, Satoshi; Donnelly, Patrick E.; Liang, Ying; Deng, Xiang‐Hua; Rodeo, Scott A.

doi:10.1016/j.arthro.2018.04.022

Cited by 39 publications

(32 citation statements)

References 31 publications

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“…Approaches including stem cells, bioactive factors, scaffolds, and other biophysical therapies have been used to promote the regeneration of fibrocartilage. 8,23,40,44,46 However, the parasympathetic nervous system and its major neurotransmitter ACh have not been studied in this field.…”

Section: Discussionmentioning

confidence: 99%

The Enhancement Effect of Acetylcholine and Pyridostigmine on Bone-Tendon Interface Healing in a Murine Rotator Cuff Model

et al. 2021

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Background: How to improve rotator cuff healing remains a challenge. Little is known about the effect of the parasympathetic transmitter acetylcholine (ACh) and the acetylcholinesterase inhibitor pyridostigmine (PYR), both of which have anti-inflammatory properties, in the healing process of rotator cuff injury. Hypothesis: ACh and PYR could enhance bone-tendon interface healing in a murine model of rotator cuff repair. Study Design: Controlled laboratory study. Methods: A total of 160 C57BL/6 mice underwent unilateral rotator cuff repair surgery. Fibrin gel (FG) was used as a drug carrier. The mice were randomly assigned to 4 groups with 40 mice per group: FG group (received FG alone), 10-5 M ACh group (received FG containing 10-5 M ACh), 10-6 M ACh group (received FG containing 10-6 M ACh), and PYR group (received FG containing 25 µg of PYR). Ten mice in each group were euthanized at 2, 4, 8, and 12 weeks postoperatively. Histologic, immunohistochemical, and biomechanical evaluations were performed for analysis. Results: Histologically, fibrocartilage-like tissue was shown at the repaired site. The proteoglycan content of the 10-5 M ACh group was significantly increased compared with the FG group at 4 weeks. M2 macrophages were identified at the repaired site for all groups at 2 and 4 weeks. At 8 weeks, M2 macrophages withdrew back to the tendon in the FG group, but a number of M2 macrophages were retained at the repaired sites in the ACh and PYR groups. Biomechanically, failure load and stiffness of the ACh and PYR groups were significantly higher than those of the FG group at 4 weeks. The stiffness of the ACh and PYR groups was significantly increased compared with the FG group at 8 weeks ( P < .001 for all). At 12 weeks, most of the healing properties of the ACh and PYR groups were not significantly different compared with the FG group. Conclusion: ACh and PYR enhanced the early stage of bone-tendon insertion healing after rotator cuff repair. Clinical Relevance: These findings imply that ACh and PYR could serve as potential therapeutic strategies for rotator cuff healing.

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Section: Discussionmentioning

confidence: 99%

The Enhancement Effect of Acetylcholine and Pyridostigmine on Bone-Tendon Interface Healing in a Murine Rotator Cuff Model

et al. 2021

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“…The operated mice were randomly allocated to 1 of 3 groups: control (n=40), rhBMP-4 (n=40), and noggin (n=40), intervened with brin sealant, brin sealant containing rhBMP-4 (Bio-tool, Beijing), and brin sealant containing noggin (Huabio, Hangzhou), respectively. Due to the ineffectivity of brin sealant to rotator cuff repair in a rodent model [15], the natural healing group was cancelled in this study. Animals were housed in cages and allowed unrestrained cage activity after surgery.…”

Section: Methodsmentioning

confidence: 99%

“…Toluidine blue-fast green (Sigma-Aldrich, St. Louis, MO). H&E stained sections were used for the histological description of healing of BTI, and semi-quantitative analysis for cell density around the tendon to bone interface [15]. Toluidine blue O/fast green (TB) stained sections were used for semiquantitative analysis for the brocartilage zone thickness using the ImageJ software (National Institutes of Health, Bethesda, Maryland) [18].…”

Section: Histomorphometric 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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“…Numerous studies have been conducted to induce fibrocartilage regeneration and enhance tendon bone connection following routine rotator cuff repair. 1 However, a promising method is still awaited.…”

Section: See Related Article On Page 1834mentioning

confidence: 99%

Editorial Commentary: Make Use of the Native Insertion Structure in Rotator Cuff Repair

Zhao

2020

Arthroscopy: The Journal of Arthroscopic & Related Surgery

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Kartogenin Enhances Collagen Organization and Mechanical Strength of the Repaired Enthesis in a Murine Model of Rotator Cuff Repair

Abstract: These findings have implications for improving the structural integrity of the repaired enthesis and potentially reducing the retear rate after rotator cuff repair, which can ultimately lead to improvements in clinical outcomes.

Cited by 39 publications

References 31 publications

The Enhancement Effect of Acetylcholine and Pyridostigmine on Bone-Tendon Interface Healing in a Murine Rotator Cuff Model

The Enhancement Effect of Acetylcholine and Pyridostigmine on Bone-Tendon Interface Healing in a Murine Rotator Cuff Model

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

Editorial Commentary: Make Use of the Native Insertion Structure in Rotator Cuff Repair

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