Expression of mitochondrial TSPO and FAM173B is associated with inflammation and symptoms in patients with painful knee osteoarthritis

Objectives To characterize the expression profiles of two nuclear-encoded mitochondrial genes previously associated with chronic pain, the translocator protein (TSPO) and family with sequence similarity 173B (FAM173B), in different knee compartments from patients with painful knee OA. Also, to examine their association with the joint expression of inflammatory cytokines/chemokines and clinical symptoms. Methods The study was performed on 40 knee OA patients and 19 postmortem (PM) controls from which we collected the knee tissues: articular cartilage (AC), synovial membrane (SM) and subchondral bone (SB). Quantitative real-time polymerase chain reaction was used to determine the relative mRNA levels of TSPO, FAM173B, and inflammatory mediators IL6, IL8, IL10, IL12, MCP1, CCL11 and CCL17. OA patients rated their pain intensity (visual analogue scale), severity of knee-related outcomes (KOOS) and pain sensitivity assessed by pressure algometry. Results The gene expression of TSPO in SM was elevated in OA patients compared with control subjects while there were no group differences in AC and SB. Expression of FAM173B was reduced in SM but elevated in SB in OA patients compared with controls. The expression of TSPO and FAM173B in SM and SB was associated with the expression of inflammatory substances, but not in AC. Synovial expression of TSPO correlated with lower pain intensity and FAM173B with increased pressure pain sensitivity in OA. Conclusion Our results suggest that altered expression of TSPO and FAM173B is associated with joint expression of inflammatory mediators and with clinical symptoms indicating the relevance for the pathophysiology of knee OA

Biomarker of extracellular matrix remodelling C1M and proinflammatory cytokine interleukin 6 are related to synovitis and pain in end-stage knee osteoarthritis patients

Little is known about local and systemic biomarkers in relation to synovitis and pain in end-stage osteoarthritis (OA) patients. We investigated the associations between the novel extracellular matrix biomarker, C1M, and local and systemic interleukin 6 (IL-6) with synovitis and pain. Serum C1M, plasma, and synovial fluid IL-6 (p-IL-6, sf-IL-6) were measured in 104 end-stage knee OA patients. Contrast-enhanced magnetic resonance imaging was used to semiquantitatively assess an 11-point synovitis score; pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Neuropathic Pain Questionnaire (NPQ). Linear regression was used to investigate associations between biomarkers and synovitis, and biomarkers and pain while controlling for age, sex, and body mass index. We also tested whether associations between biomarkers and pain were confounded by synovitis. We found sf-IL-6 was associated with synovitis in the parapatellar subregion (B = 0.006; 95% confidence interval [CI] 0.003-0.010), and no association between p-IL-6 and synovitis. We also observed an association between C1M and synovitis in the periligamentous subregion (B = 0.013; 95% CI 0.003-0.023). Furthermore, sf-IL-6, but not p-IL-6, was significantly associated with pain, WOMAC (B = 0.022; 95% CI 0.004-0.040), and NPQ (B = 0.043; 95% CI 0.005-0.082). There was no association between C1M and WOMAC pain, but we did find an association between C1M and NPQ (B = 0.229; 95% CI 0.036-0.422). Lastly, synovitis explained both biomarker-NPQ associations, but not the biomarker-WOMAC association. These results suggest that C1M and IL-6 are associated with synovitis and pain, and synovitis is an important confounding variable when studying biomarkers and neuropathic features in OA patients