Hung Jun, Al-Nakkash Layla, Broderick Tom L, Castro Monica, Plochocki Jeffrey H
1Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308 USA.
2Department of Physiology, Midwestern University, Glendale, AZ 85308 USA.
Diabetol Metab Syndr. 2019 Jan 24;11:8. doi: 10.1186/s13098-019-0402-5. eCollection 2019.
Leptin is an adipokine that regulates energy homeostasis and is also needed for normal bone growth and maintenance. Mutation in the 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.
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.
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).
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.
瘦素是一种调节能量平衡的脂肪因子，也是正常骨骼生长和维持所必需的。ob/ob小鼠模型所具有的该基因突变会导致肥胖症和2型糖尿病的发生，同时还会使四肢骨骼长度缩短以及骨折风险增加。然而，肥胖糖尿病青少年的四肢骨骼长度与生长板软骨结构之间的关系尚未完全明确。在此，我们检验了瘦素缺乏会影响幼年ob/ob小鼠生长板软骨微观结构这一假说。
对10周龄的瘦型和肥胖、瘦素缺乏（ob/ob）雌性小鼠的胫骨生长板软骨结构进行比较。我们使用共聚焦激光扫描显微镜，以0.2μm的间隔评估生长板软骨Z轴堆叠中深度为80 - 100μm的三维组织学差异。对幼年瘦型和ob/ob小鼠进行组织形态计量学比较。
我们发现，与瘦型小鼠相比，肥胖小鼠的胫骨长度和生长板高度显著降低（P < 0.05）。与瘦型小鼠相比，肥胖小鼠生长板软骨中的软骨细胞柱数量也更少，软骨细胞体积减小（P < 0.05）。
这些数据有助于阐明肥胖糖尿病幼年小鼠生长板软骨结构与骨骼健康之间的关系。我们的研究结果表明肥胖和糖尿病可能会对生长板软骨结构产生不利影响。
