Macrophage proliferation distinguishes 2 subgroups of knee osteoarthritis patients

Wood, M. J., Leckenby, A., Reynolds, G., Spiering, R., Pratt, A. G., Rankin, K. S., Isaacs, J. D., Haniffa, M. A., Milling, S. and Hilkens, C. M.U. (2019) Macrophage proliferation distinguishes 2 subgroups of knee osteoarthritis patients. JCI Insight, 4(2), e125325. (doi: 10.1172/jci.insight.125325) (PMID:30674730) (PMCID:PMC6413777)

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Abstract

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.

Item Type:Articles
Additional Information:This work was funded by Versus Arthritis (formally Arthritis Research UK) (grant no. 20298) and the JGW Patterson (JGWP) Foundation. This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 654882.
Keywords:Immunology, inflammation, macrophages, osteoarthritis, rheumatology.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Milling, Professor Simon
Authors: Wood, M. J., Leckenby, A., Reynolds, G., Spiering, R., Pratt, A. G., Rankin, K. S., Isaacs, J. D., Haniffa, M. A., Milling, S., and Hilkens, C. M.U.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:JCI Insight
Publisher:American Society for Clinical Investigation
ISSN:2379-3708
ISSN (Online):2379-3708
Published Online:24 January 2019
Copyright Holders:Copyright © 2019 American Society for Clinical Investigation
First Published:First published in JCI Insight 4(2):e125325
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190682Rheumatoid Arthritis Centre of Excellence (RACE - Towards a Cure)Iain McInnesVersus Arthritis (ARTRESUK)MP20298III - Immunology