Affiliation:
1. Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
2. Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA
3. Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, OH, USA
4. Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
Abstract
Objective 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. Design 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. Results 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]. Conclusion Initial findings suggests the presence of OA patient subgroups that could define opportunities for more targeted patient-specific approaches to prevention and treatment.
Subject
Physical Therapy, Sports Therapy and Rehabilitation,Biomedical Engineering,Immunology and Allergy