The role of mitochondrial DNA in bone/cartilage diseases

Skeletons, as a human sports scaffold, provide attachment points for muscle and ligament attachment, and store significant quantities of calcium and phosphate. The aetiology of bone-related diseases is multifactorial, involving a complex interplay between osteoblasts and osteoclasts, as well as immune system abnormalities. These factors can result in impaired motor function and physical discomfort. Recent studies have indicated an association between mitochondrial DNA (mtDNA) abnormalities and the development of bone and cartilage diseases. The level of mtDNA in body fluid is expected to become a potential diagnostic marker to evaluate the degree of bone destruction and the prognosis of complications. The mtDNA copy number abnormalities, mtDNA mutations, and mtDNA leakage contribute to the deterioration of bone and cartilage-related diseases. The increase in mtDNA copy number has been demonstrated to provide more energy for the proliferation of tumour cells. Conversely, a loss of mtDNA copy number gives rise to abnormal mitochondrial function. The coupling efficiency of oxidative phosphorylation and reactive oxygen species production is modulated by different mtDNA haplotypes, thereby impacting the energy supply required for osteoblast proliferation and differentiation. mtDNA leakage induces inflammatory cytokines via interferon-related pathways and delays fracture healing. The restoration of mtDNA copy number through repair of mitochondrial biogenesis, the reduction of mtDNA leakage, or the inhibition of downstream inflammatory pathways is expected to rescue bone and cartilage-related diseases caused by mtDNA abnormalities.