School of Medicine and Centre for Molecular and Medical Research, Deakin University, Waurn Ponds, Geelong, Australia.
Orthopaedic Department, Barwon Health, Geelong, Australia.
J Orthop Res. 2020 Oct;38(10):2280-2289. doi: 10.1002/jor.24686. Epub 2020 Apr 17.
Adhesive capsulitis (AC) is a disabling condition of the shoulder joint affecting 2 to 5% of the general population. Our understanding of the molecular mechanisms is limited. The present study aimed to determine potential biomarkers of AC through transcriptomic analysis. This multi-centre study investigated patients undergoing arthroscopic capsulotomy surgery for resistant AC compared to those undergoing arthroscopic stabilization surgery for glenohumeral instability (control). Tissue samples were harvested from the anterior capsule during surgery. Total RNA was extracted and RNA-sequencing-based transcriptomics were performed. A number of genes deemed differentially expressed in RNA-sequencing analysis were validated using real-time reverse transcription polymerase chain reaction (RT-PCR). Baseline characteristics of the AC group (n = 22) were; mean age 52.7 years (SD: 10.2), 73% female, and Oxford Shoulder Score 19.6 (SD: 8.0), compared with the control group (n = 26), average age 23.9 years (SD: 5.2), 15% female, and Oxford Shoulder Score 39.0 (SD: 7.4). Transcriptomic analysis with false discovery rate correction and log fold change cut-off of ±1.5 revealed 545 differentially expressed genes in AC relative to control. Bioinformatic analyses were carried out to identify biological processes and pathways enriched in this dataset. Real-time RT-PCR using two different normalization processes confirmed increased expression of matrix metallopeptidase 13 (MMP13) and platelet-derived growth factor subunit B (PDGFB), in patients with AC, while tumor necrosis factor α (TNFA) expression was reduced. These findings provide a comprehensive assessment of transcriptional changes associated with AC that give insights into the aetiology of the disease and provides a resource for molecular targets to better diagnose and treat this condition.
粘连性肩关节囊炎（AC）是一种影响 2%至 5%普通人群的肩关节失能性疾病。我们对其分子机制的了解有限。本研究旨在通过转录组分析确定粘连性肩关节囊炎的潜在生物标志物。这项多中心研究比较了接受关节镜下囊切开术治疗抵抗性粘连性肩关节囊炎的患者与接受关节镜下稳定术治疗肩盂肱关节不稳定的患者（对照组）。在手术中从前关节囊中采集组织样本。提取总 RNA 并进行基于 RNA 测序的转录组学分析。使用实时逆转录聚合酶链反应（RT-PCR）验证了 RNA 测序分析中差异表达的一些基因。粘连性肩关节囊炎组（n=22）的基线特征为：平均年龄 52.7 岁（标准差：10.2），73%为女性，牛津肩评分 19.6（标准差：8.0），而对照组（n=26）的平均年龄为 23.9 岁（标准差：5.2），15%为女性，牛津肩评分 39.0（标准差：7.4）。经假发现率校正和 ±1.5 的对数倍数变化截止值的转录组分析显示，粘连性肩关节囊炎组相对于对照组有 545 个差异表达基因。对该数据集进行生物信息学分析，以确定富集的生物学过程和途径。使用两种不同的归一化过程进行实时 RT-PCR 验证，证实粘连性肩关节囊炎患者的基质金属蛋白酶 13（MMP13）和血小板衍生生长因子亚单位 B（PDGFB）表达增加，而肿瘤坏死因子α（TNFA）表达减少。这些发现提供了对与粘连性肩关节囊炎相关的转录变化的全面评估，深入了解了疾病的病因，并为更好地诊断和治疗这种疾病提供了分子靶标。
