Fig. 8

A proposed model that nano-sized CB particles (Printex 90) resulted in dysfunctional mitochondria and thus inhibited osteogenesis of MSCs. Upon Printex 90 treatment, PGC1α, Nrf1 and TFAM were down-regulated followed by the relative lower copy number of mtDNA, indicating decreased mitochondrial biogenesis. Mitochondria dynamics including fusion and fission were also damaged as demonstrated by the suppressed expression of dynamics related factors, including Mfn1, Mfn2, Opa1, Drp1 and Fis1. Additionally, the accumulation of Parkin in mitochondria and PINK1 in total cell demonstrated increased mitophagy. In the meantime, mitochondrial functions were impaired, including decreased ATP production, depolarization of mitochondria and abnormal respiration. Therefore, the osteogenesis of MSCs was inhibited, demonstrated by the down-regulation of Runx2, Alp and B glap, and the poor mineralization. Collectively, CB Printex 90 could induce mitochondrial dysfunction and result in increased mitophagy and suppressed mitochondrial biogenesis and dynamics. Ultimately, the osteogenesis of MSCs was inhibited