Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA.
Cartilage. 2022 Jan-Mar;13(1):19476035221074003. doi: 10.1177/19476035221074003.
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 (P, CTPs/million cells plated), CTP concentration, [CTP], CTPs/mg)) were assessed using -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 ( = 0.23, = 0.026), JSW ( = 0.28, = 0.007), KL ( = 0.26, = 0.012), GAG/mg cartilage tissue ( = -0.31, = 0.007), and SYN-derived [Cell] ( = 0.25, = 0.049) were weak but significant predictors of OA severity. Cartilage-derived [Cell] ( = 0.38, < 0.001) and ( = 0.9, < 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.
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）鉴定 OA 患者亚群表型；（2）利用临床、组织和细胞水平的指标，确定 OA 严重程度和软骨源性干细胞/祖细胞浓度的预测因子。
从 90 例全膝关节置换术患者中收集软骨、滑膜（SYN）和髌下脂肪垫（IPFP）。采用临床指标（患者人口统计学、基于 X 线的关节间隙宽度（JSW）、Kellgren 和 Lawrence 评分（KL））、组织学指标（软骨组织学分级、糖胺聚糖（GAGs））和基于细胞的指标（软骨、SYN 和 IPFP 来源的细胞浓度[Cell]，细胞/mg）评估细胞浓度、连接组织祖细胞（CTP）流行率（P，培养的百万细胞中的 CTP 数）、CTP 浓度、[CTP]、CTP/mg）。采用 -均值聚类和线性回归模型进行评估。
鉴定出 4 个患者亚群。簇 1 和簇 2 由较年轻、较高体重指数（BMI）的患者组成，他们的软骨更健康，其中簇 1 的软骨、SYN 和 IPFP 中 CTP 含量较高，而簇 2 的软骨、SYN 和 IPFP 中 [CTP]含量较低。簇 3 和簇 4 由较年长、BMI 较低的患者组成，他们的软骨病变严重，其中簇 3 的 SYN 和 IPFP 中 [CTP]含量较低，但软骨中 [CTP]含量较高，而簇 4 的 SYN 和 IPFP 中 [CTP]含量较高，但软骨中 [CTP]含量较低。年龄（ = 0.23， = 0.026）、JSW（ = 0.28， = 0.007）、KL（ = 0.26， = 0.012）、软骨组织 GAG/mg（ = -0.31， = 0.007）和 SYN 来源的 [Cell]（ = 0.25， = 0.049）是 OA 严重程度的弱但有统计学意义的预测因子。软骨来源的 [Cell]（ = 0.38， < 0.001）和 （ = 0.9， < 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 患者亚群的存在为制定更具针对性的患者特异性预防和治疗方法提供了机会。
