Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes.

ABSTRACT: 3-Deazaneplanocin A (DZNep) is an inhibitor of S-Adenosyl-L-Homocysteine Hydrolase (SAHH) known to inhibit EZH2, a histone methylase upregulated during osteoarthritis. In this study, we assessed its effects in human articular chondrocytes. Anti-inflammatory effects were assessed by Nitric Oxide (NO), Prostaglandin E2 (PGE2) and Metalloprotease (MMP) release in IL-1β-stimulated chondrocytes. MAPK and NFκB activation was analyzed by western blotting. Differentially expressed genes (DEG) regulated by DZNep were identified by whole-transcriptome microarray. DZNep inhibited SAHH activity and was not toxic. It counteracted NO, PGE2 and MMP release, and reduced MAPK activation induced by IL-1β. By whole-transcriptome analysis, we identified that DNZep counteracts the effect of IL-1β on the expres

SUBMITTER: Aury-Landas J 

PROVIDER: S-EPMC5526903 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature