Leptin-deficient mice have altered three-dimensional growth plate histomorphometry

Abstract

Abstract Background Leptin is an adipokine that regulates energy homeostasis and is also needed for normal bone growth and maintenance. Mutation in the lep gene, which characterizes the ob/ob mouse model, results in the development of obesity and type 2 diabetes mellitus, as well as reduced limb bone length and increased fracture risk. However, the relationship between limb bone length and growth plate cartilage structure in obese diabetic adolescents is incompletely understood. Here, we tested the hypothesis that leptin deficiency affects the microstructure of growth plate cartilage in juvenile ob/ob mice. Methods Tibial growth plate cartilage structure was compared between lean and obese, leptin-deficient (ob/ob) female mice aged 10 weeks. We used confocal laser scanning microscopy to assess 3D histological differences in Z stacks of growth plate cartilage at 0.2 µm intervals, 80–100 µm in depth. Histomorphometric comparisons were made between juvenile lean and ob/ob mice. Results We found obese mice have significantly reduced tibial length and growth plate height in comparison with lean mice (P < 0.05). Obese mice also have fewer chondrocyte columns in growth plate cartilage with reduced chondrocyte cell volumes relative to lean mice (P < 0.05). Conclusions These data help explicate the relationship between growth plate cartilage structure and bone health in obese diabetic juvenile mice. Our findings suggest obesity and diabetes may adversely affect growth plate cartilage structure.

Keywords

• Obesity
• Leptin
• Ob/ob mice
• Bone
• Cartilage
• Chondrocytes