α‐Solanine attenuates chondrocyte pyroptosis to improve osteoarthritis via suppressing NF‐κB pathway

Abstract

Abstractα‐Solanine has been shown to exhibit anti‐inflammatory and anti‐tumour properties; however, its efficacy in treating osteoarthritis (OA) remains ambiguous. The study aimed to evaluate the therapeutic effects of α‐solanine on OA development in a mouse OA model. The OA mice were subjected to varying concentrations of α‐solanine, and various assessments were implemented to assess OA progression. We found that α‐solanine significantly reduced osteophyte formation, subchondral sclerosis and OARSI score. And it decreased proteoglycan loss and calcification in articular cartilage. Specifically, α‐solanine inhibited extracellular matrix degradation by downregulating collagen 10, matrix metalloproteinase 3 and 13, and upregulating collagen 2. Importantly, α‐solanine reversed chondrocyte pyroptosis phenotype in articular cartilage of OA mice by inhibiting the elevated expressions of Caspase‐1, Gsdmd and IL‐1β, while also mitigating aberrant angiogenesis and sensory innervation in subchondral bone. Mechanistically, α‐solanine notably hindered the early stages of OA progression by reducing I‐κB phosphorylation and nuclear translocation of p65, thereby inactivating NF‐κB signalling. Our findings demonstrate the capability of α‐solanine to disrupt chondrocyte pyroptosis and sensory innervation, thereby improving osteoarthritic pathological progress by inhibiting NF‐κB signalling. These results suggest that α‐solanine could serve as a promising therapeutic agent for OA treatment.