Tiron Has Negative Effects on Osteogenic Differentiation via Mitochondrial Dysfunction in Human Periosteum-Derived Cells

Int J Mol Sci. 2022 Nov 14;23(22):14040. doi: 10.3390/ijms232214040.

Abstract

Tiron is a potent antioxidant that counters the pathological effects of reactive oxygen species (ROS) production due to oxidative stress in various cell types. We examined the effects of tiron on mitochondrial function and osteoblastic differentiation in human periosteum-derived cells (hPDCs). Tiron increased mitochondrial activity and decreased senescence-associated β-galactosidase activity in hPDCs; however, it had a detrimental effect on osteoblastic differentiation by reducing alkaline phosphatase (ALP) activity and alizarin red-positive mineralization, regardless of H2O2 treatment. Osteoblast-differentiating hPDCs displayed increased ROS production compared with non-differentiating hPDCs, and treatment with tiron reduced ROS production in the differentiating cells. Antioxidants decreased the rates of oxygen consumption and ATP production, which are increased in hPDCs during osteoblastic differentiation. In addition, treatment with tiron reduced the levels of most mitochondrial proteins, which are increased in hPDCs during culture in osteogenic induction medium. These results suggest that tiron exerts negative effects on the osteoblastic differentiation of hPDCs by causing mitochondrial dysfunction.

Keywords: mitochondria; osteoblastic differentiation; periosteum-derived cells; tiron.

MeSH terms

  • 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
  • Antioxidants
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Mitochondria
  • Osteogenesis*
  • Periosteum*
  • Reactive Oxygen Species

Substances

  • 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • Antioxidants

Grants and funding

This study was supported by the National Research Foundation of Korea (2019M3A9E2066346, 2019R1F1A1061185), the Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korean government (the Ministry of Science and ICT, the Ministry of Health and Welfare) (22C0602L1) and a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI14C1277).