Sun Yaying, Lin Jinrong, Luo Zhiwen, Zhang Yuhan, Chen Jiwu
Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
J Inflamm Res. 2021 Mar 23;14:1055-1068. doi: 10.2147/JIR.S304555. eCollection 2021.
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.
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.
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.
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.
系统性炎症性疾病对肩袖修复术后继发性冻结肩（sFS）具有预后意义；然而，系统性炎症如何影响sFS仍不清楚。本研究的目的是观察sFS患者术前血清和非sFS患者血清对小鼠肩袖的影响，以及对体外巨噬细胞和成纤维细胞的影响。
术前收集连续队列中接受肩袖修复术患者的血清样本。肩袖修复术后3个月，确定发生sFS的患者（S组）。还挑选了年龄和性别匹配的无sFS对照患者的血清样本（非S组）。首先，在肩袖修复术的小鼠模型中，通过组织学和生物力学方法观察血清对肩袖纤维化的影响。其次，研究血清对巨噬细胞极化和成纤维细胞活化的作用，并确定潜在的相关信号通路。最后，对血清中炎症和纤维化相关细胞因子进行定量分析。
在我们的队列中，所有患者术前肩部活动范围均正常。7例患者在术后3个月发生sFS。选择7例匹配的无sFS患者作为对照。两组基本特征的组间差异无统计学意义。与非S组血清相比，S组血清在肩袖修复术后显著诱导小鼠肩部细胞增多、关节囊增厚和活动范围受限。与非S组血清相比，S组样本显著促进THP-1人巨噬细胞向M2极化以及人关节囊来源成纤维细胞的活化。同时，巨噬细胞和成纤维细胞中的Smad3和p-Smad3显著上调。另一方面，S组和非S组血清中炎症和纤维化相关细胞因子水平无显著差异。
尽管该队列中的所有患者术前活动范围均正常，但肩袖修复术后3个月发生sFS的患者术前血清可作为术后肩袖纤维化的触发因素。这种作用可能与其促进巨噬细胞向M2表型极化和成纤维细胞活化有关。
