Ultrastructural Evidence of Mitochondrial Dysfunction in Osteomyelitis Patients

Abstract

Osteomyelitis is a difficult-to-treat disease with high chronification rates. First studies suggest increases in mitochondrial fission and mitochondrial dysfunction as possible contributors to the accumulation of intracellular reactive oxygen species and thereby to the cell death of infected bone cells. The aim of the present study is to analyze the ultrastructural impact of bacterial infection on osteocytic and osteoblastic mitochondria. Human infected bone tissue samples were visualized via light microscopy and transmission electron microscopy. Osteoblasts, osteocytes and their mitochondria were analyzed histomorphometrically and compared with the control group of noninfectious human bone tissue samples. The results depicted swollen hydropic mitochondria including depleted cristae and a decrease in matrix density in the infected samples. Furthermore, perinuclear clustering of mitochondria could also be observed regularly. Additionally, increases in relative mitochondrial area and number were found as a correlate for increased mitochondrial fission. In conclusion, mitochondrial morphology is altered during osteomyelitis in a comparable way to mitochondria from hypoxic tissues. This gives new perspectives on the treatment strategies since the manipulation of mitochondrial dynamics may improve bone cell survival as a potential new target for the therapy of osteomyelitis.

Comprehensive Gene Analysis Reveals Cuproptosis-Related Gene Signature Associated with M2 Macrophage in Staphylococcus aureus-Infected Osteomyelitis

“… 29–31 A recent study by Tsvetkov et al 2022, 32 identified a new cell death pathway, cuproptosis, characterized by intracellular copper accumulation that triggers lipid peroxidation, mitochondrial enzyme aggregation, and destabilization of iron-sulfur (Fe-S) cluster proteins, leading to cell death. Additionally, Mendelsohn et al 2023, 33 observed mitochondrial dysfunction in patients with chronic osteomyelitis, linking it to the accumulation of intracellular reactive oxygen species that induce osteoblast cell death. Interestingly, another study found that using an inhibitor that targets the Programmed cell death 1/Programmed cell death ligand 1 (PD-1/PD-L1) pathway significantly reduced mitochondrial autophagy in F4/80 macrophages in S. aureus -infected osteomyelitis, which in turn decreased bone destruction in affected mice.…”