Carbon black suppresses the osteogenesis of mesenchymal stem cells: the role of mitochondria.

BACKGROUND: The rapid increase in carbon black poses threats to human health. We evaluated the effect of CB (Printex 90) on the osteogenesis of bone-marrow-derived mesenchymal stem cells (MSCs). Mitochondria play an important role in the osteogenesis of MSCs and are potential targets of nanomaterials, so we studied the role of mitochondria in the CB Printex 90-induced effects on osteogenesis. RESULTS: Low doses of Printex 90 (3 ng/mL and 30 ng/mL) that did not cause deleterious effects on MSCs' viability significantly inhibited osteogenesis of MSCs. Printex 90 caused down-regulation of osteoblastic markers, reduced activity of alkaline phosphatase (ALP), and poor mineralization of osteogenically induced MSCs. Cellular ATP production was decreased, mitochondrial respiration was impaired with reduced expression of ATPase, and the mitochondrial membrane was depolarized. The quantity and quality of mitochondria are tightly controlled by mitochondrial biogenesis, mitochondrial dynamics and mitophagy. The transcriptional co-activator and transcription factors for mitochondrial biogenesis, PGC-1α, Nrf1 and TFAM, were suppressed by Printex 90 treatment, suggesting that decreased biogenesis was caused by Printex 90 treatment during osteogenesis. Mitochondrial fusion and fission were significantly inhibited by Printex 90 treatment. PINK1 accumulated in Printex 90-treated cells, and more Parkin was recruited to mitochondria, indicating that mitophagy increased to remove the damaged mitochondria. CONCLUSIONS: This is the first report of the inhibitory effects of CB on the osteogenesis of MSCs and the involvement of mitochondria in CB Printex 90-induced suppression of MSC osteogenesis.

The Role of Mitochondria in Methamphetamine-induced inhibitory effects on osteogenesis of Mesenchymal Stem Cells.

Methamphetamine (METH) abuse causes significant physical, psychological, and social concerns. Therefore, in this study, we investigated its effects on osteogenic differentiation of mesenchymal stem cells (MSCs). We found that METH dose-dependently affected MSCs viability. Upon osteogenic induction, the 3 and 30 µmol/l METH dosages without deleterious effects on MSCs viability resulted in the down-regulation of osteoblastic marker genes (Alp, Bglap, and Runx2), suppression of the protein expression of RUNX2, and decreased ALP activity and mineralization ability. Mitochondria are essential during osteogenesis of MSCs. Our analysis on mitochondrial function revealed that METH decreased ATP production, suppressed the oxygen consumption rate, and depolarized the mitochondrial membrane potential, but it had no significant effects on the protein expression of the five complexes on the respiratory chain. Additionally, METH could impair mitochondrial biogenesis, as demonstrated by decreased mtDNA and down-regulated biogenesis factors. Mitochondrial fusion regulators were also decreased at the mRNA and protein levels. However, mitochondrial fission and mitophagy were not affected. In conclusion, our study revealed that exposure to METH could result in decreased mitochondrial biogenesis and fusion as well as mitochondrial dysfunction, and thus it suppressed the osteogenesis of MSCs.