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Microarray analysis of bone marrow lesions in osteoarthritis demonstrates upregulation of genes implicated in osteochondral turnover, neurogenesis and inflammation

Kuttapitiya, A; Assi, L; Laing, K; Hing, C; Mitchell, P; Whitley, G; Harrison, O; Howe, FA; Ejindu, V; Heron, C; et al. Kuttapitiya, A; Assi, L; Laing, K; Hing, C; Mitchell, P; Whitley, G; Harrison, O; Howe, FA; Ejindu, V; Heron, C; Sofat, N (2017) Microarray analysis of bone marrow lesions in osteoarthritis demonstrates upregulation of genes implicated in osteochondral turnover, neurogenesis and inflammation. Annals of the Rheumatic Diseases, 76 (10). pp. 1764-1773. ISSN 1468-2060 https://doi.org/10.1136/annrheumdis-2017-211396
SGUL Authors: Howe, Franklyn Arron Laing, Kenneth Sofat, Nidhi Whitley, Guy St John Assi, Lena

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Abstract

Objective Bone marrow lesions (BMLs) are well described in osteoarthritis (OA) using MRI and are associated with pain, but little is known about their pathological characteristics and gene expression. We evaluated BMLs using novel tissue analysis tools to gain a deeper understanding of their cellular and molecular expression. Methods We recruited 98 participants, 72 with advanced OA requiring total knee replacement (TKR), 12 with mild OA and 14 non-OA controls. Participants were assessed for pain (using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) and with a knee MRI (using MOAKS). Tissue was then harvested at TKR for BML analysis using histology and tissue microarray. Results The mean (SD) WOMAC pain scores were significantly increased in advanced OA 59.4 (21.3) and mild OA 30.9 (20.3) compared with controls 0.5 (1.28) (p<0.0001). MOAKS showed all TKR tissue analysed had BMLs, and within these lesions, bone marrow volume was starkly reduced being replaced by dense fibrous connective tissue, new blood vessels, hyaline cartilage and fibrocartilage. Microarray comparing OA BML and normal bone found a significant difference in expression of 218 genes (p<0.05). The most upregulated genes included stathmin 2, thrombospondin 4, matrix metalloproteinase 13 and Wnt/Notch/catenin/chemokine signalling molecules that are known to constitute neuronal, osteogenic and chondrogenic pathways. Conclusion Our study is the first to employ detailed histological analysis and microarray techniques to investigate knee OA BMLs. BMLs demonstrated areas of high metabolic activity expressing pain sensitisation, neuronal, extracellular matrix and proinflammatory signalling genes that may explain their strong association with pain.

Item Type: Article
Additional Information: This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/
Keywords: Arthritis & Rheumatology, 1103 Clinical Sciences, 1107 Immunology, 1117 Public Health And Health Services
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Neuroscience (INCCNS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Vascular (INCCVA)
Journal or Publication Title: Annals of the Rheumatic Diseases
ISSN: 1468-2060
Dates:
DateEvent
1 October 2017Published
13 July 2017Published Online
5 June 2017Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
M11-F2The Rosetrees' TrustUNSPECIFIED
CRNNIHR Health Services and Delivery Research (HS&DR) programmeUNSPECIFIED
URI: http://openaccess.sgul.ac.uk/id/eprint/108899
Publisher's version: https://doi.org/10.1136/annrheumdis-2017-211396

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