Macrophage proliferation distinguishes 2 subgroups of knee osteoarthritis patients
| Autor: | Simon Milling, Gary Reynolds, Adam Leckenby, John D. Isaacs, Kenneth S. Rankin, Matthew J. Wood, Rachel Spiering, Catharien M. U. Hilkens, Muzlifah Haniffa, Arthur G. Pratt |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CD86 business.industry Cartilage Inflammation General Medicine Osteoarthritis medicine.disease Pathogenesis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Medicine Macrophage Proliferation Marker medicine.symptom business Macrophage proliferation Research Article |
| Zdroj: | JCI insight. 4(2) |
| ISSN: | 2379-3708 |
| Popis: | Osteoarthritis (OA) is a leading cause of disability, globally. Despite an emerging role for synovial inflammation in OA pathogenesis, attempts to target inflammation therapeutically have had limited success. A better understanding of the cellular and molecular processes occurring in the OA synovium is needed to develop novel therapeutics. We investigated macrophage phenotype and gene expression in synovial tissue of OA and inflammatory-arthritis (IA) patients. Compared with IA, OA synovial tissue contained higher but variable proportions of macrophages (P < 0.001). These macrophages exhibited an activated phenotype, expressing folate receptor-2 and CD86, and displayed high phagocytic capacity. RNA sequencing of synovial macrophages revealed 2 OA subgroups. Inflammatory-like OA (iOA) macrophages are closely aligned to IA macrophages and are characterized by a cell proliferation signature. In contrast, classical OA (cOA) macrophages display cartilage remodeling features. Supporting these findings, when compared with cOA, iOA synovial tissue contained higher proportions of macrophages (P < 0.01), expressing higher levels of the proliferation marker Ki67 (P < 0.01). These data provide new insight into the heterogeneity of OA synovial tissue and suggest distinct roles of macrophages in pathogenesis. Our findings could lead to the stratification of OA patients for suitable disease-modifying treatments and the identification of novel therapeutic targets. |
| Databáze: | OpenAIRE |
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