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A Simple Critical-sized Femoral Defect Model in Mice
Published on: March 15, 2015
Decreased osteoclastogenesis, osteoblastogenesis and low bone mass in a mouse model of type 2 diabetes
Fei Xu1, Yonghui Dong1, Xin Huang1
1Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
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.
Insights
Type 2 diabetes mellitus (T2DM) impairs bone metabolism, leading to reduced bone formation and resorption. This study in diabetic mice shows decreased bone mass and weakened biomechanics, suggesting T2DM contributes to osteoporosis.
Area of Science:
- Endocrinology
- Orthopedics
- Metabolic Diseases
Background:
- The impact of type 2 diabetes mellitus (T2DM) on bone health remains debated.
- Investigating T2DM's role in osteoporosis is crucial for understanding its systemic effects.
Purpose of the Study:
- To determine if T2DM causes osteoporosis.
- To elucidate the mechanisms by which T2DM affects bone physiology.
Main Methods:
- Utilized a KK-Ay mouse model of T2DM, comparing them to non-diabetic C57BL/6 mice.
- Assessed bone parameters including weight, bone mineral density, osteoblast/osteoclast activity (von Kossa, TRAP staining, ALP/TRAP activity), and bone biomechanics (ultimate load).
- Analyzed gene expression related to bone metabolism.
Main Results:
- Diabetic mice showed hyperglycemia, hyperinsulinemia, increased body/fat weight, and reduced bone weight and bone mineral density in the femur, tibia, and lumbar vertebra.
- Impaired osteoblastogenesis and osteoclastogenesis were observed in diabetic mice.
- The ultimate load of the tibia was significantly lower in diabetic mice compared to controls.
Conclusions:
- T2DM negatively impacts bone metabolism, characterized by reduced osteoblast and osteoclast activity.
- These findings suggest T2DM contributes to decreased bone mass and potentially osteoporosis.
- The study highlights the detrimental effects of T2DM on skeletal integrity.
