Protective effects of alogliptin against TNF-α-induced degradation of extracellular matrix in human chondrocytes

Abstract

Osteoarthritis (OA) is a common debilitating disease most prevalent among the elderly population worldwide. Excessive degradation of the articular extracellular matrix is a pivotal event in the development of OA. Preventative treatments against the destruction of type II collagen and aggrecan, the two main components of the articular extracellular matrix, may serve as a novel therapy against the progression of OA. In the current study, we investigated whether the DPP-4 inhibitor alogliptin could prevent degradation of the articular extracellular matrix in human primary chondrocytes. Pretreatment with alogliptin successfully prevented degradation of type II collagen and aggrecan in a dose-dependent manner by reducing increased expression of MMP-1, -3, and -13 as well as ADAMTS-4 and -5 induced by treatment with TNF-α. Furthermore, pretreatment with alogliptin also reduced TNF-α-induced expression of IKKα/β, IκBα and NF-κB in human primary chondrocytes. This suggests that DPP-4 inhibitors such as alogliptin may be used as an effective preventative therapy against continued destruction of the articular extracellular matrix in OA.