Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy.

ABSTRACT:

Background

Ageing-related failure of homeostasis mechanisms contributes to articular cartilage degeneration and osteoarthritis (OA), for which disease-modifying treatments are not available. Our objective was to identify molecules to prevent OA by regulating chondrocyte senescence and autophagy.

Methods

Human chondrocytes with IL-6 induced senescence and autophagy suppression and SA-β-gal as a reporter of senescence and LC3 as reporter of autophagic flux were used to screen the Prestwick Chemical Library of approved drugs. Preclinical cellular, tissue and blood from OA and blood from OA and ageing models were used to test the efficacy and relevance of activating PPARα related to cartilage degeneration.

Findings

Senotherapeutic molecules with pro-autophagic activity we

SUBMITTER: Nogueira-Recalde U 

PROVIDER: S-EPMC6642320 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature