Decreased osteoclastogenesis, osteoblastogenesis and low bone mass in a mouse model of type 2 diabetes

Mol Med Rep. 2014 Oct;10(4):1935-41. doi: 10.3892/mmr.2014.2430. Epub 2014 Jul 30.

Abstract

The effect of type 2 diabetes mellitus (T2DM) on bone is controversial. Therefore, the present study investigated whether T2DM causes osteoporosis and explored the underlying mechanisms involved in this process. The effects of T2DM on bone physiology were analyzed in a mouse model of T2DM; KK/Upj‑Ay/J (KK‑Ay) mice develop diabetes after 8 weeks and exhibit stable diabetes symptoms and signs after 10 weeks when fed a KK‑Ay mouse maintenance fodder. Diabetic mice exhibited hyperglycemia, hyperinsulinemia and increased body and fat pad weight in comparison with C57BL/6 non-diabetic mice. Furthermore, diabetic mice demonstrated low bone weight and bone mineral density in the femur, tibia and fifth lumbar vertebra. Using von Kossa and tartrate-resistant acid phosphatase (TRAP) staining, alkaline phosphatase and TRAP activity analyses and gene profiling it was demonstrated that osteoblastogenesis and osteoclastogenesis were impaired in diabetic mice. To evaluate the bone biomechanics, the ultimate load of the bone was analyzed. It was found that the ultimate load of the tibia in diabetic mice was lower than that in the controls. The results from the present study suggest that bone metabolism is impaired in T2DM, resulting in decreased osteoblastogenesis, osteoclastogenesis and bone mass.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / metabolism
  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Density
  • Bone and Bones / chemistry
  • Bone and Bones / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology*
  • Disease Models, Animal
  • Femur / cytology
  • Isoenzymes / metabolism
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Osteogenesis*
  • Spine / diagnostic imaging
  • Tartrate-Resistant Acid Phosphatase
  • Tibia / diagnostic imaging
  • Tomography, X-Ray Computed

Substances

  • Isoenzymes
  • Alkaline Phosphatase
  • Acid Phosphatase
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase