Genetic and Epigenetic Insights into Osteoarthritis Pathogenesis; Spotlighting STAT3 and miR-452-3p as Illuminating Examples

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disease, characterized by progressive degradation and loss of articular cartilage, subchondral bone sclerosis, inflammation, and osteophyte formation. Edema, chronic pain, and limited joint movement are the major signs of OA. Recent studies have shown that it affects 240 million aged people globally, and about 10% of males and 18% of women over the age of 60. Because of this, it is now the main factor in pain, disability, and decreased adult work performance throughout the world. OA can be regarded as a multifactorial disease, with several factors including aging, genetic predisposition, epigenetic control, inflammation, obesity, and trauma being involved in its pathophysiology. Signal transducer and activator of transcription 3 (STAT3) has been described as one of the critical factors involved in the initiation and development of inflammatory responses in OA. Previous studies have provided evidence that microRNAs (miRNAs) play a major role in the regulation of STAT3 expression through binding to the 3′ untranslated region (3′UTR) of STAT3 mRNA