Fenofibrate decreases the bone quality by down regulating Runx2 in high-fat-diet induced Type 2 diabetes mellitus mouse model

Lipids Health Dis. 2017 Oct 13;16(1):201. doi: 10.1186/s12944-017-0592-5.

Abstract

Background: This study is to investigate the effect of fenofibrate on the bone quality of Type 2 diabetes mellitus (T2DM) mouse model.

Methods: T2DM mouse model was induced by high-fat-diet, and the mice were treated with fenofibrate (100 mg/kg) (DIO-FENO) or PBS (DIO-PBS) for 4 weeks. The bone microstructure and biomechanical properties of femora were analyzed by micro-CT and 3-Point bending test. The protein expression was detected by immunohistochemical staining and Western blot. The cell apoptosis was evaluated by TUNEL staining. The Bcl2, caspase 3, and osteoblast marker genes were detected by RT-qPCR.

Results: The biomechanical properties of bones from DIO-FENO group were significantly lower than those in the control and DIO-PBS groups. Besides, the trabecular number was lower than those of the other groups, though the cortical porosity was decreased compared with that of DIO-PBS group because of the increase of apoptotic cells. The expression of osteocalcin and collagen I were decreased after treatment with fenofibrate in T2DM mice. Moreover, the cell viability was decreased after treated with different concentrations of fenofibrate, and the expression of Runx2 decreased after treated with high dose of fenofibrate.

Conclusion: Fenofibrate decreases the bone quality of T2DM mice through decreasing the expression of collagen I and osteocalcin, which may be resulted from the down regulation of Runx2 expression.

Keywords: Bone quality; Fenofibrate; Runx2; Type 2 diabetes mellitus.

MeSH terms

  • Animals
  • Bone Density / drug effects*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Core Binding Factor Alpha 1 Subunit / antagonists & inhibitors
  • Core Binding Factor Alpha 1 Subunit / genetics*
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Dyslipidemias / etiology
  • Dyslipidemias / genetics*
  • Dyslipidemias / metabolism
  • Dyslipidemias / pathology
  • Fenofibrate / adverse effects*
  • Gene Expression Regulation
  • Humans
  • Hypolipidemic Agents / adverse effects*
  • Mice
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Porosity / drug effects
  • Primary Cell Culture
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • X-Ray Microtomography

Substances

  • Collagen Type I
  • Core Binding Factor Alpha 1 Subunit
  • Hypolipidemic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Runx2 protein, mouse
  • Osteocalcin
  • Bcl2 protein, mouse
  • Casp3 protein, mouse
  • Caspase 3
  • Fenofibrate