MnTBAP inhibits bone loss in ovariectomized rats by reducing mitochondrial oxidative stress in osteoblasts

J Bone Miner Metab. 2020 Jan;38(1):27-37. doi: 10.1007/s00774-019-01038-4. Epub 2019 Sep 6.

Abstract

The development of postmenopausal osteoporosis is thought to be closely related to oxidative stress. Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a novel superoxide dismutase (SOD) mimetic, could protect osteoblasts from cytotoxicity and dysfunction caused by oxidative stress. However, it is still unclear whether MnTBAP has effect on the development of postmenopausal osteoporosis. Here, we demonstrated that MnTBAP can inhibit bone mass loss and bone microarchitecture alteration, and increase the number of osteoblasts while reducing osteoclasts number, as well as improve the BMP-2 expression level in ovariectomized rat model. Additionally, MnTBAP can also prevent oxidative stress status up-regulation induced by ovariotomy and hydrogen peroxide (H2O2). Furthermore, MnTBAP reduced the effect of oxidative stress on osteoblasts differentiation and increased BMP-2 expression levels with a dose-dependent manner, via reducing the levels of mitochondrial oxidative stress in osteoblasts. Taken together, our findings provide new insights that MnTBAP inhibits bone loss in ovariectomized rats by reducing mitochondrial oxidative stress in osteoblasts, and maybe a potential drug in postmenopausal osteoporosis therapy.

Keywords: MnTBAP; Osteoblast; Ovariectomized rat; Oxidative stress; Postmenopausal osteoporosis.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Resorption / drug therapy*
  • Bone Resorption / prevention & control*
  • Bone and Bones / drug effects
  • Bone and Bones / pathology
  • Cell Differentiation / drug effects
  • Disease Models, Animal
  • Female
  • Hydrogen Peroxide / toxicity
  • Metalloporphyrins / pharmacology
  • Metalloporphyrins / therapeutic use*
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Organ Size / drug effects
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Ovariectomy*
  • Oxidative Stress* / drug effects
  • Rats, Sprague-Dawley
  • Up-Regulation / drug effects

Substances

  • Bone Morphogenetic Protein 2
  • Metalloporphyrins
  • manganese(III)-tetrakis(4-benzoic acid)porphyrin
  • Hydrogen Peroxide