Abstract
Chondrocyte dysfunction occurs during the development of osteoarthritis (OA), typically resulting from a deleterious increase in oxidative stress. Accordingly, strategies for arresting oxidative stress-induced chondrocyte dysfunction may lead to new potential therapeutic targets for OA treatment. Forkhead box O (FoxO) transcription factors have recently been shown to play a protective role in chondrocyte dysfunction through the regulation of inflammation, autophagy, aging, and oxidative stress. They also regulate growth, maturation, and matrix synthesis in chondrocytes. In this review, we discuss the recent progress made in the field of oxidative stress-induced chondrocyte dysfunction. We also discuss the protective role of FoxO transcription factors as potential molecular targets for the treatment of OA. Understanding the function of FoxO transcription factors in the OA pathology may provide new insights that will facilitate the development of next-generation therapies to prevent OA development and to slow OA progression.
Highlights
Osteoarthritis (OA), a leading cause of disability, is a prevalent rheumatic disease characterized by articular cartilage breakdown [1]
In experimental murine OA, the decreased expression of autophagy markers is correlated with the loss of extracellular matrix (ECM) in cartilage, decreased autophagy in osteoarthritic chondrocytes, and an increase in apoptosis [28,32]
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Summary
Osteoarthritis (OA), a leading cause of disability, is a prevalent rheumatic disease characterized by articular cartilage breakdown [1]. FoxOs govern oxidative defenses such as manganese-dependent superoxide dismutase (MnSOD), catalase (CAT), and the DNA repair enzyme growth arrest and DNA damage 45 (GADD45) [13,14] They can regulate protein degradation mediated by the ubiquitin–proteasome system [15] and the autophagic/lysosomal pathway [16]. FoxOs have recently been shown to regulate cellular senescence signals [23], chondrocyte autophagy [20], chondrocyte maturation [24], and aging [6]. All of these physiological or pathological conditions contribute to the development of OA [25,26]. We will discuss alterations in FoxO expression and activation during OA development, the role of FoxOs in aging, and the inhibition of oxidative stress and inflammation in chondrocytes
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