The Serum from Patients with Secondary Frozen Shoulder Following Rotator Cuff Repair Induces Shoulder Capsule Fibrosis and Promotes Macrophage Polarization and Fibroblast Activation
Yaying Sun,* Jinrong Lin,* Zhiwen Luo,* Yuhan Zhang, Jiwu Chen Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiwu ChenDepartment of Sports Medicine, Huashan Hospital, Fud...
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2021
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| Acceso en línea: | https://doaj.org/article/eb3384372b634c0fbae899d1cfbf02ba |
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| Sumario: | Yaying Sun,* Jinrong Lin,* Zhiwen Luo,* Yuhan Zhang, Jiwu Chen Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiwu ChenDepartment of Sports Medicine, Huashan Hospital, Fudan University, 12# Middle Wulumuqi Road, Jing’an District, Shanghai, 200040, People’s Republic of ChinaFax +86 21 52888255Email jeevechen@gmail.comPurpose: Disorders with systematic inflammation were prognostic for secondary frozen shoulder (sFS) following rotator cuff repair (RCR); however, how systematic inflammation affects sFS remains unclear. The aim of this study was to observe the effect of pre-operative serum from patients with sFS and the serum from those without on shoulder capsule in mice, and on macrophages and fibroblasts in vitro.Methods: Serum samples of a consecutive cohort of patients for RCR were collected pre-operatively. Three months after RCR, patients who developed sFS (Group S) were identified. Serum samples from gender- and age-matched controls without sFS (group NS) were also picked out. Firstly, the effect of serum on shoulder capsule fibrosis was observed histologically and biomechanically in a mouse model of RCR. Secondly, the roles of the serum on macrophage polarization and fibroblast activation were investigated, and the potentially involved signaling pathways were identified. Finally, inflammation and fibrosis-related cytokines in serum were quantified.Results: In our cohort, all patients had free pre-operative shoulder range of motion. Seven patients developed sFS at 3 months after surgery. Seven matched patients without sFS were selected as control. The inter-group difference of basic characteristics was not significant. Compared to the serum of group NS, the serum of group S significantly induced hypercellularity, capsular thickening, and range of motion deficiency in mice shoulders after RCR. Compared to the serum of group NS, samples of group S significantly promoted M2 polarization of THP-1 human macrophages and the activation of human capsule-derived fibroblasts. Meanwhile, Smad3 and p-Smad3 in macrophages and fibroblasts were significantly up-regulated. On the other hand, levels of inflammation and fibrosis-related cytokines were not significantly different between serum in group S and group NS.Conclusion: Although all patients in this cohort had free range of motion pre-operatively, the pre-operative serum from patients with sFS at 3 months after RCR could act as a trigger of shoulder capsule fibrosis post-operatively. This effect may be related to its promotion on macrophage polarization to M2 phenotype and fibroblast activation.Keywords: rotator cuff, secondary frozen shoulder, serum, macrophage, fibroblast |
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