原发性骨关节炎(OA)的临床异质性是理解发病机制和制定靶向治疗策略的主要挑战。本研究旨在(1)确定OA患者亚组表型和(2)确定OA严重程度和软骨来源的干/祖细胞浓度的预测因子,组织-,和细胞级指标。
软骨,收集90例全膝关节置换术患者的滑膜(SYN)和髌下脂肪垫(IPFP)。临床指标(患者人口统计学,基于射线照相的关节间隙宽度(JSW),凯尔格伦和劳伦斯得分(KL)),组织指标(软骨组织病理学分级,糖胺聚糖(GAG)和基于细胞的指标(软骨-,SYN-,和IPFP衍生的细胞浓度([细胞],细胞/毫克),结缔组织祖细胞(CTP)患病率(PCTP,CTP/百万个细胞铺板),CTP浓度,[CTP],CTP/mg))采用k均值聚类和线性回归模型进行评估。
确定了四个患者亚组。集群1和2由年轻人组成,高体重指数(BMI)患者的软骨更健康,其中第1簇在软骨中具有高CTP,SYN,和IPFP,第2簇软骨中的[CTP]较低,SYN,和IPFP。集群3和4由较旧的,低BMI的患病软骨患者,其中集群3在SYN中具有低[CTP],IPFP,但软骨中的[CTP]高,并且群集4在SYN中具有较高的[CTP],IPFP但软骨中[CTP]低。年龄(r=0.23,P=0.026),JSW(r=0.28,P=0.007),KL(r=0.26,P=0.012),GAG/mg软骨组织(r=-0.31,P=0.007),和SYN衍生的[Cell](r=0.25,P=0.049)是OA严重程度的弱预测因子,但具有重要意义。软骨来源的[细胞](r=0.38,P<0.001)和PCTP(r=0.9,P<0.001)是软骨来源的[CTP]的中度/强预测因子。
初步研究结果表明,OA患者亚组的存在可以确定更有针对性的患者特异性预防和治疗方法的机会。
Clinical heterogeneity of primary osteoarthritis (OA) is a major challenge in understanding pathogenesis and development of targeted therapeutic strategies. This study aims to (1) identify OA patient subgroups phenotypes and (2) determine predictors of OA severity and cartilage-derived stem/progenitor concentration using clinical-, tissue-, and cell- level metrics.
Cartilage, synovium (SYN) and infrapatellar fatpad (IPFP) were collected from 90 total knee arthroplasty patients. Clinical metrics (patient demographics, radiograph-based joint space width (JSW), Kellgren and Lawrence score (KL)), tissue metrics (cartilage histopathology grade, glycosaminoglycans (GAGs)) and cell-based metrics (cartilage-, SYN-, and IPFP-derived cell concentration ([Cell], cells/mg), connective tissue progenitor (CTP) prevalence (PCTP, CTPs/million cells plated), CTP concentration, [CTP], CTPs/mg)) were assessed using k-mean clustering and linear regression model.
Four patient subgroups were identified. Clusters 1 and 2 comprised of younger, high body mass index (BMI) patients with healthier cartilage, where Cluster 1 had high CTP in cartilage, SYN, and IPFP, and Cluster 2 had low [CTP] in cartilage, SYN, and IPFP. Clusters 3 and 4 comprised of older, low BMI patients with diseased cartilage where Cluster 3 had low [CTP] in SYN, IPFP but high [CTP] in cartilage, and Cluster 4 had high [CTP] in SYN, IPFP but low [CTP] in cartilage. Age (r = 0.23, P = 0.026), JSW (r = 0.28, P = 0.007), KL (r = 0.26, P = 0.012), GAG/mg cartilage tissue (r = -0.31, P = 0.007), and SYN-derived [Cell] (r = 0.25, P = 0.049) were weak but significant predictors of OA severity. Cartilage-derived [Cell] (r = 0.38, P < 0.001) and PCTP (r = 0.9, P < 0.001) were moderate/strong predictors of cartilage-derived [CTP].
Initial findings suggests the presence of OA patient subgroups that could define opportunities for more targeted patient-specific approaches to prevention and treatment.