Assessment of Clinical, Tissue, and Cell-Level Metrics Identify Four Biologically Distinct Knee Osteoarthritis Patient Phenotypes.
Assessment of Clinical, Tissue, and Cell-Level Metrics Identify Four Biologically Distinct Knee Osteoarthritis Patient Phenotypes.
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DOI：
10.1177/19476035221074003
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发表时间：
2022-01
期刊：
影响因子：
2.8
通讯作者：
Muschler, George F.
中科院分区：
文献类型：
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作者：
Mantripragada, Venkata P.;Csorba, Alexander;Bova, Wesley;Boehm, Cynthia;Piuzzi, Nicolas S.;Bullen, Jennifer;Midura, Ronald J.;Muschler, George F.
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患者亚群表型；(2)通过临床、组织和细胞水平指标确定OA严重程度和软骨源性干/祖细胞浓度的预测因子。收集90例全膝关节置换术患者的软骨、滑膜（SYN）和髌下脂肪垫（IPFP）。临床指标（患者人口统计学、基于x线片的关节间隙宽度（JSW）、Kellgren和Lawrence评分（KL））、组织指标（软骨组织病理学分级、糖胺聚糖（GAGs））和细胞指标（软骨、SYN和ipfp衍生的细胞浓度（[cell]，细胞/mg）、结缔组织祖细胞（CTP）发病率（PCTP，细胞/百万细胞）、CTP浓度，[CTP]，细胞/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。第1类和第2类由较年轻、高身体质量指数（BMI）、软骨较健康的患者组成，其中第1类患者的软骨、SYN和IPFP的CTP较高，第2类患者的软骨、SYN和IPFP的CTP较低。第3组和第4组为年龄较大、BMI较低的软骨病变患者，其中第3组SYN、IPFP [CTP]较低，但软骨的[CTP]较高；第4组SYN、IPFP [CTP]较高，但软骨的[CTP]较低。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-derived [Cell] （r = 0.25, P = 0.049）是OA严重程度的弱但显著的预测因子。软骨源性[细胞]（r = 0.38, P < 0.001）和PCTP （r = 0.9, P < 0.001）是软骨源性[CTP]的中/强预测因子。初步研究结果表明，OA患者亚组的存在可以为更有针对性的患者特异性预防和治疗方法提供机会。
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.
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影响因子：
--
作者：
Lotz, Martin K.;Otsuki, Shuhei;Grogan, Shawn P.;Sah, Robert;Terkeltaub, Robert;D'Lima, Darryl
通讯作者：
D'Lima, Darryl
影响因子：
7.2
作者：
Gillooly, James F.;Hein, Andrew;Damiani, Rachel
通讯作者：
Damiani, Rachel
影响因子：
4.6
作者：
Chou, Ching-Heng;Jain, Vaibhav;Kraus, Virginia B.
通讯作者：
Kraus, Virginia B.
影响因子：
12.7
作者：
Chen D;Shen J;Zhao W;Wang T;Han L;Hamilton JL;Im HJ
通讯作者：
Im HJ
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ