Ethyl Linoleate Ameliorates Synovial Cell Proliferation and Inflammatory Cell Infiltration in Rheumatoid Arthritis Through DKK1/Wnt-OPG Signal Axis and Autophagy

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease affecting synovial joints. Jinwu Jiangu Capsules (JJC) has been shown to be effective in treating RA. However, the primary active components and the underlying molecular mechanisms of JJC in RA treatment remain unclear. This study investigates how the monomers of JJC regulate the DKK1/Wnt-OPG signaling axis and autophagy in RA, both in vivo and in vitro. Evaluate the antiarthritis effects of JJC using a Type II collagen-induced arthritis (CIA) rat model. Histopathological analysis is conducted using HE staining, while qPCR, Western blot, ELISA, and GFP-LC3 are used to assess the DKK1/Wnt-OPG signaling pathway and autophagy status. Key components of the capsule are identified through network pharmacology. The effects of these components on osteoblasts are evaluated using CCK-8, alizarin red staining, ALP activity assay, EdU staining, MDC detection, and TRAP staining. JJC effectively reduced the expression of DKK1, RANKL, β-catenin, and p-β-catenin, while increasing the levels of autophagy-related proteins such as Beclin-1, LC3, and Atg5, thus positively affecting the progression of RA. Network pharmacology analysis revealed that ethyl linoleate (EL), a key component of JJC, targeted DKK1. RA model rats showed a dose-dependent response to EL. It significantly reduced cell proliferation and inflammatory cell infiltration in knee joint synovium and improved tissue structure. EL lowered DKK1 and RANKL levels in knee joint synovium and bone tissue, and increased OPG and LC3 expression. Additionally, it enhanced ALP activity and survival of osteoblasts, promoted cell proliferation and autophagy, protected osteoblast function, and inhibited the differentiation of PBMCs into osteoclasts, demonstrating its potential therapeutic effects on RA pathology. EL, a key component of JJC, exhibits significant therapeutic potential and positive effects in the treatment of RA by influencing the DKK1/Wnt-OPG signaling axis and autophagic processes.