Abstract
BackgroundInflammation is associated with the onset and progression of osteoarthritis in multiple joints. It is well known that mechanical properties differ between different joints, however, it remains unknown if the inflammatory process is similar/distinct in patients with hip vs. knee OA. Without complete understanding of the role of any specific cytokine in the inflammatory process, understanding the ‘profile’ of inflammation in a given patient population is an essential starting point. The aim of this study was to identify serum cytokine profiles in hip Osteoarthritis (OA), and investigate the association between cytokine concentrations and clinical measurements within this patient population and compare these findings to knee OA and healthy control cohorts.MethodsIn total, 250 serum samples (100 knee OA, 50 hip OA and 100 control) and 37 synovial fluid samples (8 knee OA, 14 hip OA and 15 control) were analyzed using a multiplex ELISA based approach. Synovial biopsies were also obtained and examined for specific cytokines. Pain, physical function and activity within the hip OA cohort were examined using the HOOS, SF-36, HHS and UCLA outcome measures.ResultsThe three cohorts showed distinct serum cytokine profiles. EGF, FGF2, MCP3, MIP1α, and IL8 were differentially expressed between hip and knee OA cohorts; while FGF2, GRO, IL8, MCP1, and VEGF were differentially expressed between hip OA and control cohorts. Eotaxin, GRO, MCP1, MIP1β, VEGF were differentially expressed between knee OA and control cohorts. EGF, IL8, MCP1, MIP1β were differentially expressed in synovial fluid from a sub-set of patients from each cohort. Specifically within the hip OA cohort, IL-6, MDC and IP10 were associated with pain and were also found to be present in synovial fluid and synovial membrane (except IL-6) of patients with hip OA.ConclusionOA may include different inflammatory subtypes according to affected joints and distinct inflammatory processes may drive OA in these joints. IL6, MDC and IP10 are associated with hip OA pain and these proteins may be able to provide additional information regarding pain in hip OA patients.
Highlights
Inflammation is associated with the onset and progression of osteoarthritis in multiple joints
While 5 cytokines were differentially expressed between knee and hip OA cohorts (Fig. 1), 3 cytokines (GRO: growth-regulated oncogene aka C-X-C motif ligand 1/CXCL1, MCP1: monocyte chemoattractant protein aka C-C motif ligand 2/CCL2 and Vascular endothelial growth factor (VEGF): vascular endothelial growth factor) were conserved in both hip and knee OA cohorts when compared to the control cohort (Fig. 1)
Synovial fluid and serum shared common cytokines that were differentially expressed between cohorts: Epidermal growth factor (EGF) differed between hip OA and knee OA; IL8 was different between hip OA and control; MCP1, MIP1β differed between knee OA and control (Fig. 2)
Summary
Inflammation is associated with the onset and progression of osteoarthritis in multiple joints. It is well known that mechanical properties differ between different joints, it remains unknown if the inflammatory process is similar/distinct in patients with hip vs knee OA. Most of the common OA biochemical markers (collagen fragments, cartilage oligomeric matrix protein (COMP), etc.) have been tested on both knee and hip cohorts, but only a very few studies looked at both joints and run comparisons [17]. It is well known that mechanical properties differ between joints (knee vs hip) [20, 21], but as far as we are aware only two studies have directly compared between cohorts of hip and knee OA patients: the effectiveness of bone metabolism for OA prognostic [22] and the difference of association between COMP and OA symptoms [23]. Neither of them compared the absolute concentration of biochemical markers between two phenotypes
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