Ghrelin suppresses apoptosis and autophagy in osteoarthritis synovial cells by modulating the ADORA2B/PI3K/Akt/mTOR signaling pathway

Abstract

Given the pivotal role that apoptosis and autophagy play in the pathogenesis of osteoarthritis (OA), the current study aims to examine the regulatory effects of ghrelin on these processes via the ADORA2B/PI3K/Akt/mTOR signaling pathway. Serum levels of ghrelin were measured in both OA patients and healthy controls using an ELISA kit. Cell proliferation was evaluated through the Cell Counting Kit-8 (CCK-8) assay, while Western blot analysis was utilized to determine the expression levels of autophagy-related proteins (LC3II/I, BECLIN-1) and apoptosis markers (BAX, Bcl-2), as well as to assess the activation status of the PI3K/Akt/mTOR signaling pathway in OA synovial cells. These analyses were performed under conditions of ADORA2B and mTOR silencing, as well as in control settings. The results revealed that ghrelin expression was significantly reduced in the serum of OA patients. Furthermore, ghrelin was found to enhance synovial cell proliferation while simultaneously inhibiting apoptosis and autophagy, as evidenced by lowered expression levels of LC3/I, BECLIN-1, and BAX, alongside an increase in Bcl-2 expression. This modulation occurred through the regulation of the PI3K/Akt/mTOR signaling pathway mediated by ADORA2B. These findings underscore the role of ghrelin in the progression of osteoarthritis by influencing synovial cell activity through the ADORA2B/PI3K/Akt/mTOR pathway, thus laying the groundwork for investigating targeted therapeutic strategies in clinical practice.