Intra-articular injection of stigmasterol loaded nanoparticles is effective in inhibiting joints destruction in an osteoarthritis rat model

Abstract

Abstract Stigmasterol, a plant-derived sterol, sharing structural similarity with cholesterol, has demonstrated anti-osteoarthritis (OA) properties, attributed to its antioxidant and anti-inflammatory capabilities. Given that OA often arises in weight bearing or overused joints, prolonged localized treatment effectively targets inflammatory aspects of the disease. This research explored the impact of stigmasterol-loaded nanoparticles delivered via intra-articular injections in an OA rat model. Employing mesoporous silica nanomaterials (MSNs) combined with β-cyclodextrin (β-CD) as a vehicle, stigmasterol was loaded in conjunction with tannic acid, forming stigmasterol/β-CD-MSNs to facilitate a sustained stigmasterol release. The study employed RAW 264.7 cells to examine the in vitro cytotoxicity and anti-inflammatory effect of stigmasterol/β-CD-MSNs. For in vivo experimentation, we used healthy control rats and monosodium iodoacetate (MIA)-induced OA rats, separated into five groups, varying the injection substances. In vitro findings indicated that stigmasterol/β-CD-MSNs suppressed the mRNA expression of key pro-inflammatory mediators such as interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-3 in a dose-dependent manner. In vivo experiments revealed a substantial decrease in the mRNA levels of pro-inflammatory factors in the stigmasterol(50 µg)/β-CD-MSN group compared to the others. Macroscopic, radiographic, and histological evaluations established that intra-articular injections of stigmasterol/β-CD-MSNs inhibited cartilage degeneration and subchondral bone deterioration. Therefore, in a chemically induced OA rat model, intra-articular stigmasterol delivery was associated with reduction in both local and systemic inflammatory responses, alongside a slowdown in joint degradation and arthritic progression.