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Macrophage proliferation distinguishes 2 subgroups of knee osteoarthritis patients

Lookup NU author(s): Dr Matthew Wood, Adam Leckenby, Dr Gary ReynoldsORCiD, Dr Rachel Spiering, Dr Arthur PrattORCiD, Dr Kenneth RankinORCiD, Professor John IsaacsORCiD, Professor Muzlifah Haniffa, Dr Simon Milling, Professor Catharien Hilkens

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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.

Publication metadata

Author(s): Wood MJ, Leckenby A, Reynolds G, Spiering R, Pratt AG, Rankin KS, Isaacs JD, Haniffa MA, Milling S, Hilkens CM

Publication type: Article

Publication status: Published

Journal: JCI Insight

Year: 2019

Volume: 4

Issue: 2

Pages: e125325

Print publication date: 24/01/2019

Online publication date: 24/01/2019

Acceptance date: 18/12/2018

Date deposited: 19/02/2019

ISSN (print): 2379-3708

Publisher: American Society for Clinical Investigation

URL: https://doi.org/10.1172/jci.insight.125325

DOI: 10.1172/jci.insight.125325

PubMed id: 30674730

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