Kartogenin (KGN) Reverses Intervertebral Disc Degeneration in Advanced Stages: Effects on Cell Viability, Senescence, Extracellular Matrix, and Matrix Metalloproteinases

Abstract

This study examined the effects of Kartogenin (KGN), a small molecule compound, on intervertebral disc degeneration (IDD) cells of varying degrees. Human nucleus pulposus (NP) cells were isolated from tissues with different levels of degeneration, and the influence of KGN on cell viability, senescence, extracellular matrix (ECM), and matrix metalloproteinases (MMPs) production was investigated. Mild and severe degeneration of NP cells was induced using IL-1β. KGN increased cell viability in naturally regressive NP cells, particularly in severely regressive cells. It had no effect on healthy NP cells but promoted collagen II, aggrecan, and proliferation while decreasing p16, p21, p53, collagen I, MMP3/9, and apoptosis in naturally regressive NP cells, especially at advanced degeneration stages. Furthermore, KGN effectively prevented IL-1β-induced NP degeneration, particularly at a 10 ng/mL dose. KGN delayed NP cell degeneration, with a greater impact observed at later degeneration stages. Therefore, KGN shows potential for repairing IDD in advanced stages, but higher doses should be considered for early-stage IDD.