Differential Expression of Fibrinogen Alpha and Its Potential Involvement in Osteoarthritis Pathogenesis.

ABSTRACT

The deterioration of cartilage tissue and other joint components composed of synovial tissue is a defining characteristic of osteoarthritis (OA) disease. Because of the lack of understanding of the underlying cause and important molecular pathways, there are currently no effective diagnostic or treatment methods for OA. The purpose of the study is to find a specific protein biomarker with high sensitivity and specificity in order to understand the pathophysiology of the disease and the underlying molecular pathways. We examined plasma samples of matched age and sex from OA patients (n = 150) and healthy controls (HC) (n = 70) to find proteins that were differentially expressed and validated by western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence. The results of western blotting demonstrated that the expression level of the fibrinogen alpha (FGA) protein was higher in plasma samples of osteoarthritis (OAPL) (p = 0.0343), and the ROC (receiver operating characteristic curve) curve supported the high sensitivity (95.22%) and specificity (74%) of FGA in OA plasma compared to healthy controls. FGA protein was detected to be deposited in the synovial tissue of OA patients (p = 0.0073). By activating the Toll-like receptor (TLR-4) receptor pathway in PBMCs (p = 0.04) and synovial tissue, FGA protein may be involved in the molecular mechanism of OA pathogenesis. Our findings collectively suggested that FGA, which is significantly expressed in OA plasma, synovial tissue, and PBMCs and is connected to the disease's advancement through the TLR-4 receptor, may serve as a diagnostic or disease-evolving tool for OA.