Oxidative stress modulates osteoblastic differentiation of vascular and bone cells

Free Radic Biol Med. 2001 Aug 15;31(4):509-19. doi: 10.1016/s0891-5849(01)00610-4.


Oxidative stress may regulate cellular function in multiple pathological conditions, including atherosclerosis. One feature of the atherosclerotic plaque is calcium mineral deposition, which appears to result from the differentiation of vascular osteoblastic cells, calcifying vascular cells (CVC). To determine the role of oxidative stress in regulating the activity of CVC, we treated these cells with hydrogen peroxide (H(2)O(2)) or xanthine/xanthine oxidase (XXO) and assessed their effects on intracellular oxidative stress, differentiation, and mineralization. These agents increased intracellular oxidative stress as determined by 2,7 dichlorofluorescein fluorescence, and enhanced osteoblastic differentiation of vascular cells, based on alkaline phosphatase activity and mineralization. In contrast, H(2)O(2) and XXO resulted in inhibition of differentiation markers in bone osteoblastic cells, MC3T3-E1, and marrow stromal cells, M2-10B4, while increasing oxidative stress. In addition, minimally oxidized low-density lipoprotein (MM-LDL), previously shown to enhance vascular cell and inhibit bone cell differentiation, also increased intracellular oxidative stress in the three cell types. These effects of XXO and MM-LDL were counteracted by the antioxidants Trolox and pyrrolidinedithiocarbamate. These results suggest that oxidative stress modulates differentiation of vascular and bone cells oppositely, which may explain the parallel buildup and loss of calcification, seen in vascular calcification and osteoporosis, respectively.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Calcium / metabolism
  • Cattle
  • Cell Differentiation / physiology*
  • Cell Division / drug effects
  • Cells, Cultured
  • Formazans
  • Hydrogen Peroxide / pharmacology
  • Lipoproteins, LDL / pharmacology
  • Mice
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / metabolism
  • Osteoblasts / cytology*
  • Osteoblasts / metabolism
  • Oxidative Stress / physiology*
  • Reactive Oxygen Species / metabolism
  • Superoxides / metabolism
  • Tetrazolium Salts
  • Xanthine / pharmacology
  • Xanthine Oxidase / pharmacology


  • Formazans
  • Lipoproteins, LDL
  • Reactive Oxygen Species
  • Tetrazolium Salts
  • oxidized low density lipoprotein
  • Superoxides
  • Xanthine
  • MTT formazan
  • Hydrogen Peroxide
  • Xanthine Oxidase
  • Alkaline Phosphatase
  • Calcium