Serum Levels of HMGB1, hS100A8/A9, and sRAGE in Patients with Knee and Hip Osteoarthritis: Inflammatory Biomarkers of Disease Activity.

Background/Objectives: Osteoarthritis (OA) is the most prevalent type of arthritis, primarily impacting synovial joints. While it has traditionally been viewed as resulting from mechanical wear and tear, OA is now increasingly understood as an inflammatory condition. By analysing serum concentrations of molecular patterns related to inflammatory damage (DAMPs), including high-mobility group box 1 protein (HMGB1), hS100A8/A9 proteins, and their soluble receptor for advanced glycation end products (sRAGE), it is possible to investigate the inflammatory pathogenesis of the disease. Methods: The research was conducted at Dubrava University Hospital in Zagreb, Croatia, from March 2022 to July 2024. The study analyses venous blood from 94 subjects with different degrees of knee osteoarthritis (KOA) and hip osteoarthritis (hip OA) using ELISA. The aim is to measure serum levels of DAMP biomarkers, including HMGB1, hS100A8/A9, and sRAGE. Results: Subjects with KOA exhibited higher levels of HMGB1 (21.72 ± 3.50) than those with hip OA (7.11 ± 1.46) or controls (1.64 ± 0.80), indicating a potential role for HMGB1 as a proinflammatory mediator. Lower sRAGE levels in KOA (499.97 ± 18.71) compared to controls (1273.8 ± 58.92) may suggest impaired anti-inflammatory activity. Because of possible differences in biomechanical loads and metabolic pathways, hS100A8/A9 concentrations in KOA (1227.06 ± 175.34) were greater than in hip OA (664.88 ± 38.90). Conclusions: HMGB1 exhibits proinflammatory and sRAGE anti-inflammatory activity in knee osteoarthritis (KOA) and hip OA. Their levels support an inflammatory pathogenesis of these diseases. HMGB1 and sRAGE are promising biomarkers for monitoring disease progression and could represent potential therapeutic targets.