Impact of ligustrazine on chondrocyte apoptosis in knee osteoarthritis through FAK/PI3K/Akt pathway

Abstract

Objective: To probe into the impact of ligustrazine on chondrocyte apoptosis in knee osteoarthritis (OA) and its pos­sible mechanism.

Methods: Our team extracted the human primary chondrocytes to construct the IL-113-induced chondrocyte damage model, detected the impact of ligustrazine on chondrocyte apoptosis through TUNEL and Western blot, applied Western blot to detect the impact of ligustrazine on matrix-degrading enzymes, matrix-associated proteins, as well as FAK/PI3K/ Akt pathway, using ELISA detected the impact of ligustrazine on MCP-1, IL8, PEG2 and NO levels, applied FAK/PI3K/ Akt pathway inhibitor PF573228 to inhibit FAK/PI3K/Akt pathway to detect whether the chondroprotective impact of ligustrazine was inhibited, constructed a New Zealand rabbit osteoarthritis model, applied HE staining to evaluate the impacts of ligustrazine and ligustrazine+PF573228 on cartilage histomorphology, and applied Western blot to detect the impacts of ligustrazine and ligustrazine+PF573228 on apoptotic proteins, matrix-degrading enzymes and matrix-related proteins in cartilage tissue.

Results: Ligustrazine signally inhibited IL-113-induced chondrocyte apoptosis, reduced Bax, caspase-9, caspase-3, caspase-7, MMP3, MMP13, collagen X protein expression levels, and reduced MCP-1, IL8, PEG2, and MCP-1. NO contents, promoted collagen II and aggrecan protein expression. Additionally, ligustrazine activated the FAK/PI3K/ Akt pathway, and applying PF573228 to inhibit the FAK/PI3K/Akt pathway abolished the chondroprotective impact of ligustrazine. At the in vivo level, ligustrazine activated the FAK/PI3K/Akt pathway to inhibit Bax, caspase-9, caspase-3, caspase-7, MMP3, MMP13, collagen X protein expression levels, promoted collagen II and aggrecan protein expression, and improved cartilage histomorphology.

Conclusion: Ligustrazine exerts chondroprotective impact through FAK/PI3K/Akt pathway