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Protective effects of alogliptin against TNF-α-induced degradation of extracellular matrix in human chondrocytes.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2019 Mar; Vol. 68, pp. 179-184. Date of Electronic Publication: 2019 Jan 15. - Publication Year :
- 2019
-
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.<br /> (Copyright © 2018. Published by Elsevier B.V.)
- Subjects :
- Aggrecans metabolism
Cells, Cultured
Chondrocytes metabolism
Collagen Type II metabolism
DNA-Binding Proteins physiology
Extracellular Matrix drug effects
Humans
Metalloproteases physiology
Uracil pharmacology
Chondrocytes drug effects
Dipeptidyl-Peptidase IV Inhibitors pharmacology
Piperidines pharmacology
Protective Agents pharmacology
Tumor Necrosis Factor-alpha
Uracil analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 68
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 30654307
- Full Text :
- https://doi.org/10.1016/j.intimp.2018.11.007