Mitochondrial Genome Editing to Treat Human Osteoarthritis-A Narrative Review.
Gang ZhongHenning MadryMagali CucchiariniPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- crispr cas
- genome editing
- mitochondrial dna
- knee osteoarthritis
- oxidative stress
- copy number
- endothelial cells
- induced apoptosis
- rheumatoid arthritis
- extracellular matrix
- stem cells
- genome wide
- gene expression
- induced pluripotent stem cells
- physical activity
- cell therapy
- bone marrow
- current status
- replacement therapy
- body mass index
- risk assessment
- cell proliferation
- pluripotent stem cells
- weight loss