The Correlation Of Synovium And Synovial Fluid High Mobility Group Box B1 And The Severity Of Disease In Primary Knee Osteoarthritis

Objective: The purpose of this study was to evaluate the characteristic and correlation of clinical and radiological in primary knee osteoarthritis patients. Detection the amount of and location of HMGB-1 in primary knee OA synovium. To preliminarily disusss the fuction of synovoum HMGB1 in the development of OA. We also evaluated the relationship between the level of HMGB-1 in synovial fluid with the severity of clinic symptoms and synovium pathological change with knee OA patients. To clear whether synovial HMGB1 can be a biomarker in reaction of OA severity and give us a new idea in early diagnosis. Methods: Seventy-four patients who meet the standard of primary knee OA were recruited. Western Ontario McMaster University Osteoarthritis Index(WOMAC) assessment scale and Kellgren-Lawrence(KL) grading system were applied to evaluate the clinic and radiological severity of OA patients. OA group was divided KL2/3 group(moderate group) and KL4 group(severe group) according to KL grading. Thirty-four patients who inflicted acute meniscal or cruciate ligament tears were recruited as controls. Control patients had not history of OA and KL grading was zero. Additionally, for all patients, microscopic synovitis were graded to evaluate the severity of synovium pathology from hypercellular lining layer, cellular density of subintimal stroma and inflammatory infiltrate. The location of HMGB-1 was determined in synovium by immunohistochemistry. Synovium and synovial fluid HMGB-1 levels were measured by western-blotting and Enzyme-linked immunosorbent assay(ELISA) respectively. SPSS 21.0 was applied to analyze experimental data. Results: KL grade were associated with total WOMAC score and daily activity, but were not associated with pain and stiff in knee OA paients by spearman correlation analysis. Synovium immunohistochemical analysis revealed that HMGB-1 mainly displayes a nuclear localization in controls, however, both nuclear and cytoplasmic distributions are present in OA patients. The percentage of HMGB-1-positive cells as well as cytoplasmic HMGB-1 cell population in OA patients are higher than controls(42.5% vs 39.7% and 24.0% vs 5.7%,p<0.05). Both synovium and synovial fluid HMGB-1 levels in OA patients are significantly higher than controls by western-bolt and ELISA method( p<0.05). In OA patients, HMGB-1 in KL2/3 group are higher than KL4 group( p<0.05). Additionally, synovial fluid HMGB-1 levels in OA patients are positively associated with the severity of synovitis, pain and daily activities, but not associated with stiff by spearman correlation analysis. Conclusions: Our results demonstrated that joint function in OA patients may mainly influenced by local factors,.but the mechanism of pain and stiff were complex, may be the result of local and system factors. HMGB1 was overexpression in knee OA synovium and synovial. HMGB-1 in synovium as a pro-inflammatory cytokines may play a crucial role in the progression of knee OA, mainly in the early and middle stage. The increased synovial fluid HMGB-1 levels may be a new biological markers for knee OA.