PGC-1α in osteoarthritic chondrocytes: From mechanism to target of action

Abstract

Osteoarthritis (OA) is one of the most common degenerative joint diseases, often involving the entire joint. The degeneration of articular cartilage is an important feature of OA, and there is growing evidence that the mitochondrial biogenesis master regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) exert a chondroprotective effect. PGC-1α delays the development and progression of OA by affecting mitochondrial biogenesis, oxidative stress, mitophagy and mitochondrial DNA (mtDNA) replication in chondrocytes. In addition, PGC-1α can regulate the metabolic abnormalities of OA chondrocytes and inhibit chondrocyte apoptosis. In this paper, we review the regulatory mechanisms of PGC-1α and its effects on OA chondrocytes, and introduce potential drugs and novel nanohybrid for the treatment of OA which act by affecting the activity of PGC-1α. This information will help to further elucidate the pathogenesis of OA and provide new ideas for the development of therapeutic strategies for OA.

Activation of Sirtuin3 by honokiol ameliorates alveolar epithelial cell senescence in experimental silicosis via the cGAS-STING pathway

“…Since mitochondrial DNA is bare, it is highly susceptible to oxidative damage from the attack of reactive oxygen species. Previous studies have suggested that sirt3 could enhance the activity of 8-oxo guanine DNA glycosylase-1 (OGG1) to repair oxidative damage of mtDNA by deacetylating OGG1 [ 31 ]. Therefore, we hypothesized that HKL could take effects via promoting the deacetylation activity of sirt3 to activate OGG1 repairing the oxidative damage of mtDNA.…”

Characterizing mitochondrial features in osteoarthritis through integrative multi-omics and machine learning analysis

“…PGC-1α, a master regulator of mitochondrial biogenesis, plays a protective role in cartilage. PGC-1α delays the onset and progression of OA by influencing mitochondrial biogenesis, oxidative stress, mitochondrial autophagy, and mitochondrial DNA replication in chondrocytes ( 53 ). Studies have found that mitochondrial DNA damage is present in chondrocytes of OA patients, accompanied by reduced DNA repair capacity ( 54 ).…”

Natural anti‐inflammatory products for osteoarthritis: From molecular mechanism to drug delivery systems and clinical trials

“…At the level of subcellular organelles, puerarin ameliorates mitochondrial dysfunction via the AMPK/PGC-1α signaling pathway in MIA-induced OA chondrocytes . As a transcription factor, PGC-1α regulates the cell death, metabolism, and mitochondrial dysfunction in OA chondrocytes via multiple molecular mechanisms (Wang et al, 2023), and the AMPK/PGC-1α pathway activation mainly promotes mitochondrial biogenesis in OA chondrocytes (Wang, Zhao, et al, 2015), which then ameliorates OA inflammation procession.…”