Resatovir Combined with Glycyrrhizic Acid Ameliorates Osteoarthritis and Enhances Autophagy in Chondrocytes

Abstract

Background: Osteoarthritis (OA) is a chronic disease worldwide. With resatovir usually used as an inhibitor, resatovir and glycyrrhizic acid have several pharmacological activities.Objectives: We intend to explore the mechanism underlying resatovir combined with glycyrrhizic acid in OA.Materials and Methods: After the establishment of an animal model of OA through anterior cruciate ligament transection and destabilization of the medial meniscus, the rats were subjected to intramuscular injection of resatovir combined with glycyrrhizic acid (60 mg/kg) or 5% glucose (60 mg/kg) every day for 4 weeks. During the progress, the rat movement and the bend score of knees were observed through behavioral studies. Additionally, the SKP2 gene expression and toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB)-related signaling pathways were examined, as apoptosis and autophagy were evaluated by flow cytometry.Results: With increased inflammatory cells in the model group, treatment with resatovir combined with glycyrrhizic acid significantly decreased the number of inflammatory cells. Meanwhile, the treatment resulted in decreased SKP2 expression in OA cells when hindering the migration of preosteoclast cells. Interestingly, it was observed that the bend score increased over the treatment with resatovir plus glycyrrhizic acid and TIPPI% declined dramatically. Resatovir treatment enhanced autophagy and apoptosis in OA cells and decreased pP65, P65, and LC3 expression.Conclusion: Resatovir combined with glycyrrhizic acid can inhibit the inflammatory response through decreasing SKP2 expression and induce autophagy activation in OA cells through TLR4/NF-κB signaling, thereby attenuating OA progression.

Keywords: Osteoarthritis; resatovir; glycyrrhizic acid; toll-like receptor 4/nuclear factor-κB; autophagy