Linagliptin protects human chondrogenic ATDC5 cells against advanced glycation end products (AGEs)-induced apoptosis via a mitochondria-dependent pathway.

Chondrocytes in joints are responsible for the formation and remodeling of articular cartilage. The accumulation of advanced glycation end products (AGEs) in cartilage is detrimental to the survival of chondrocytes. Linagliptin is one of the most commonly used anti-diabetes agents, and recent work indicates that it exerts an anti-inflammatory effect in different cell types. In this study, we showed that Linagliptin had a protective role in AGEs-induced chondrocyte injury. The presence of Linagliptin ameliorated AGEs-induced reactive oxygen species (ROS) induction and reduced cellular protein carboxyl content. Linagliptin mitigated AGEs-induced mitochondrial membrane potential (ΔΨm) reduction and NAPDH oxidase subunit NOX-4 induction, indicating that Linagliptin is a potent anti-ROS agent in chondrocytes. Additionally, Linagliptin inhibited AGEs-induced production of high mobility group box chromosomal protein 1 (HMGB-1), and the expression of matrix metalloproteases (MMPs)-2 and -9. Flow cytometry experimentation showed that Linagliptin inhibited AGEs-induced apoptotic subpopulation. Moreover, Linagliptin inhibited the AGEs-induced increased ratio of Bax to Bcl-2, translocation of cytochrome C from mitochondria to the cytoplasm, and release of cleaved caspase-3. Collectively, our data indicate that the anti-diabetes drug Linagliptin has a new role in rescuing chondrocyte from insult by AGEs, and may, therefore, have the potential to treat joint disorders.