The PI3K/AKT/mTOR signaling pathway in osteoarthritis: a narrative review

Abstract

Osteoarthritis (OA) is a complicated degenerative disease that affects whole joint tissue. Currently, apart from surgical approaches to treat late stage OA, effective treatments to reverse OA are not available. Thus, the mechanisms leading to OA, and more effective approaches to treat OA should be investigated. According to available evidence, the PI3K/AKT/mTOR signaling pathway is essential for normal metabolism of joint tissues, but is also involved in development of OA. To provide a wide viewpoint to roles of PI3K/ AKT/mTOR signaling pathway in osteoarthritis, a comprehensive literature search was performed using PubMed terms 'PI3K OR AKT OR mTOR' and 'osteoarthritis'. This review highlights the role of PI3K/AKT/ mTOR signaling in cartilage degradation, subchondral bone dysfunction, and synovial inflammation, and discusses how this signaling pathway affects development of the disease. We also summarize recent evidences of therapeutic approaches to treat OA by targeting the PI3K/AKT/mTOR pathway, and discuss potential challenges in developing these strategies for clinical treatment of OA.

Anti-Inflammatory and Chondroprotective Effects of Vanillic Acid and Epimedin C in Human Osteoarthritic Chondrocytes

“…Furthermore, for regeneration of damaged cartilage, it is essential to increase the chondrocytes anabolism to rebuild cartilage and restore joint function. Inflammatory cytokines including IL-1β and TNF-α initiate the development and progression of OA through activating or inhibiting different signaling pathways such as NF-κB, HMGB1, IL-1R/TLR, MAPKs, and PI3K/Akt/mTOR pathways [8][9][10][11][12][13][14][15][16][17][18]. In our previous study, we used these two inflammatory cytokines on microtissues of human primary chondrocytes to develop an inflammatory model of arthritis.…”

Insights Into the Molecular Mechanism of Deer Antler Extract Serving as a Potential Chondroprotective Agent for Articular Cartilage

“…Based on the KEGG enrichment analysis, the signi cant enriched pathways were predominantly involved in thyroid hormone signaling pathway, protein digestion and absorption, PI3K-AKT signaling pathway, nitrogen metabolism, ECM-receptor interaction and cell adhesion molecules (CAMs). Among those enriched signaling pathways, thyroid hormone signaling pathway, PI3K-AKT signaling pathway, ECM-receptor interaction and cell adhesion molecules (CAMs) have been considered to play crucial roles in articular cartilage maintenance and osteoarthritis pathogenesis [32][33][34][35]. Thus, these results suggest that DAE play potential role in regulating articular cartilage homeostasis by controling multiple functional group genes and signaling pathways.…”

Investigating the molecular control of deer antler extract on articular cartilage 

“…Based on the KEGG enrichment analysis, the signi cant enriched pathways were predominantly involved in thyroid hormone signaling pathway, protein digestion and absorption, PI3K-AKT signaling pathway, nitrogen metabolism, ECM-receptor interaction and cell adhesion molecules (CAMs). Among those enriched signaling pathways, thyroid hormone signaling pathway, PI3K-AKT signaling pathway, ECM-receptor interaction and cell adhesion molecules (CAMs) have been considered to play crucial roles in articular cartilage maintenance and osteoarthritis pathogenesis [34][35][36][37]. Thus, these results suggest that DAE play potential role in regulating articular cartilage homeostasis by controling multiple functional group genes and signaling pathways.…”