Abstract
The multifactorial pathogenesis of osteoarthritis (OA) and the diversity of its phenotypic manifestations have been subjects of discussion in recent years. This report summarizes the latest data from clinical studies regarding the pathogenesis (PG) of OA. Aspects of PG are examined, such as: the consequences of trauma, the involvement of heat shock proteins, mitochondrial dysfunction, disturbances in the JAK/STAT signaling pathway, low-grade focal inflammation, the role of different macrophage populations, telomere shortening in the aging process, and more. Special attention is given to the involvement of genetic and epigenetic factors in the multifactorial pathogenesis of osteoarthritis. These factors, through mechanisms of gene expression modulation—such as DNA methylation and demethylation, histone modifications, acetylation and deacetylation, and activation of microRNAs—contribute to either silencing or enhanced expression of genes associated with OA. In this way, fine post-transcriptional tuning is maintained, which increases resistance to chronic diseases, including OA. Knowledge of epigenetic control could provide a more in-depth, holistic understanding of the etiology and pathogenesis of OA and offer future directions for its management.
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