Abstract
Osteoarthritis (OA) is a severe, common chronic orthopaedic disorder characterised by a degradation of the articular cartilage with an incidence that increases over years. Despite the availability of various clinical options, none can stop the irreversible progression of the disease to definitely cure OA. Various mutations have been evidenced in the mitochondrial DNA (mtDNA) of cartilage cells (chondrocytes) in OA, leading to a dysfunction of the mitochondrial oxidative phosphorylation processes that significantly contributes to OA cartilage degeneration. The mitochondrial genome, therefore, represents a central, attractive target for therapy in OA, especially using genome editing procedures. In this narrative review article, we present and discuss the current advances and breakthroughs in mitochondrial genome editing as a potential, novel treatment to overcome mtDNA-related disorders such as OA. While still in its infancy and despite a number of challenges that need to be addressed (barriers to effective and site-specific mtDNA editing and repair), such a strategy has strong value to treat human OA in the future, especially using the groundbreaking clustered regularly interspaced short palindromic repeats (CRIPSR)/CRISPR-associated 9 (CRISPR/Cas9) technology and mitochondrial transplantation approaches.
Highlights
Osteoarthritis (OA) is the most prevalent chronic joint disorder that affects millions of adult individuals worldwide [1,2]
The emergence of genome editing technologies that may be applied to target the mitochondrial genome provides hope to precisely modulate mitochondrial DNA (mtDNA) genes involved in the development of OA as a means to reliably manage this disease in patients
Editing the mitochondrial genome is an emerging, attractive strategy to manage mutations in the mtDNA in OA and, subsequently, the dysfunction of the mitochondrial oxidative phosphorylation processes in OA chondrocytes that substantially contribute to the pathogenesis of this severe, highly prevalent human disorder
Summary
Osteoarthritis (OA) is the most prevalent chronic joint disorder that affects millions of adult individuals worldwide [1,2]. The emergence of genome editing technologies that may be applied to target the mitochondrial genome provides hope to precisely modulate mtDNA genes involved in the development of OA as a means to reliably manage this disease in patients. Such innovative mitochondrial treatment options for OA are being discussed in this narrative article with the goal of feasible and safe translational applications in the near future
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