Microarray analysis of bone marrow lesions in osteoarthritis demonstrates upregulation of genes implicated in osteochondral turnover, neurogenesis and inflammation. Issue 10 (13th July 2017)

• Record Type: Journal Article
• Authors: Kuttapitiya, Anasuya; Assi, Lena; Laing, Ken; Hing, Caroline; Mitchell, Philip; Whitley, Guy; Harrison, Abiola; Howe, Franklyn A; Ejindu, Vivian; Heron, Christine; Sofat, Nidhi
• Other Names: Sandhu Virinderjit author non-byline.; Moss Katie author non-byline.; Kaul Arvind author non-byline.; Kiely Patrick author non-byline.; Rolfe Debbie author non-byline.; Chis Ster Irina author non-byline.; Sheppard Mary author non-byline.
• Is Part Of: Annals of the rheumatic diseases. Volume 76:Issue 10(2017)
• Page Start: 1764
• Page End: 1773
• Publication Date: 2017-07-13
• Subjects: Knee Osteoarthritis -- Magnetic Resonance Imaging -- Inflammation -- Chondrocytes -- Chemokines; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2017-211396
• Languages: English
• ISSNs: 0003-4967

Abstract

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.