Kartogenin - A Potential Small Molecule for Managing Osteoarthritis

Abstract

There is a current need to develop novel therapeutic strategies to improve osteoarthritis (OA) outcomes by reducing joint pain, slow down the progress of cartilage degeneration and support cartilage regeneration.  In order to reduce the progression of OA, a number of small molecules with chondrogenic, anti-inflammatory, and extracellular matrix modulatory activities are being investigated as potential OA medications. Kartogenin (KGN) is one such molecule recently identified through an image-based-high-throughput screening. Since its discovery many studies have been conducted to determine its biological effects. KGN has shown to effect chondrogenesis, increase cartilage regeneration, reduce OA-induced pain, reduce inflammation and may play a role in modulating limb development. Additionally, many biomaterial based carriers have been developed for the sustained release of KGN. Lastly, several biological mechanisms of action of KGN are identified.  These include the Filamin A/CBFβ/RUNX1, Indian Hedgehog (Ihh), TGFβ/Smad Pathway for Chondrogenesis, the AKT/PI3K and TAOK1/Hippo Pathways for its anti-inflammatory effects and IL-10 mediated analgesic effect. The observed impacts on the formation of cartilage cells, maintaining a balance of anabolic and catabolic effects, decreasing inflammation, and offering pain alleviation, emphasize the potential benefits of administering KGN for treating osteoarthritis.