Tamasi Joseph A, Arey Brian J, Bertolini Donald R, Feyen Jean H M
Osteoporosis Research, Metabolic and Cardiovascular Drug Discovery PRI, Bristol-Myers Squibb Company, Pennington, New Jersey 08534, USA.
J Bone Miner Res. 2003 Sep;18(9):1605-11. doi: 10.1359/jbmr.2003.18.9.1605.
To investigate the role of leptin in bone formation, the skeleton of the obese female leptin receptor-deficient Zucker rat was examined using pQCT, microCT, and histomorphometry. A trend toward decreasing structural and bone formation parameters in these rats as they age suggest that leptin has a small positive effect on bone.
Evidence in the literature has suggested the possible role of leptin in bone formation. Leptin deficiency or leptin receptor deficiency results in higher bone mass. In an attempt to further investigate leptin's role in bone formation, we examined the skeleton of obese leptin receptor-deficient Zucker rats.
Female leptin receptor-deficient Zucker (fa/fa) rats and their homozygous (Fa/Fa) and heterozygous (Fa/fa) lean controls were used at 9 and 15 weeks of age (n = 5). Bone mineral density of the proximal tibia was measured by peripheral quantitative computed tomography (pQCT). Microcomputed tomography (microCT) was used for the analysis of trabecular architecture in the proximal tibia metaphysis and cortical bone at the tibia-fibula junction. Static and dynamic parameters of bone resorption and formation were quantitated by histomorphometry. Statistical analysis was performed by Dunnett's one-way ANOVA.
Analysis of the proximal tibia by pQCT show no significant differences in the bone mineral density of obese rats compared with their corresponding lean controls in either age group. Trabecular architecture measured by microCT indicate a trends toward decreasing bone volume (BV/TV) in the obese animals, evident by a decrease in trabecular number and thickness with an increase in trabecular separation. Histomorphometric evaluation further shows significant increases in osteoclast surface in the obese rats at both 9 and 15 weeks without a change in osteoclast number. Osteoid surface in the obese animals was also found to be decreased by 15 weeks of age. Fluorescent-based measurements of bone formation were not significantly different. Differences in the cortical compartment were not observed at either age.
Based on the observed skeletal phenotype of the Zucker (fa/fa) rat, it is suggested that leptin exerts a positive effect on bone.
为研究瘦素在骨形成中的作用，使用外周定量计算机断层扫描（pQCT）、显微计算机断层扫描（microCT）和组织形态计量学对肥胖的雌性瘦素受体缺陷型Zucker大鼠的骨骼进行了检查。随着这些大鼠年龄增长，其结构和骨形成参数呈下降趋势，这表明瘦素对骨骼有微小的正向作用。
文献中的证据表明瘦素在骨形成中可能发挥作用。瘦素缺乏或瘦素受体缺乏会导致骨量增加。为进一步研究瘦素在骨形成中的作用，我们检查了肥胖的瘦素受体缺陷型Zucker大鼠的骨骼。
使用9周龄和15周龄的雌性瘦素受体缺陷型Zucker（fa/fa）大鼠及其纯合（Fa/Fa）和杂合（Fa/fa）的瘦素对照大鼠（n = 5）。通过外周定量计算机断层扫描（pQCT）测量胫骨近端的骨密度。显微计算机断层扫描（microCT）用于分析胫骨近端干骺端的小梁结构以及胫腓关节处的皮质骨。通过组织形态计量学对骨吸收和形成的静态和动态参数进行定量分析。采用Dunnett单因素方差分析进行统计分析。
pQCT对胫骨近端的分析显示，在两个年龄组中，肥胖大鼠的骨密度与相应的瘦素对照大鼠相比均无显著差异。microCT测量的小梁结构表明，肥胖动物的骨体积（BV/TV）有下降趋势，表现为小梁数量和厚度减少，小梁间距增加。组织形态计量学评估进一步显示，肥胖大鼠在9周龄和15周龄时破骨细胞表面均显著增加，而破骨细胞数量没有变化。还发现肥胖动物的类骨质表面在15周龄时减少。基于荧光的骨形成测量无显著差异。在两个年龄组中均未观察到皮质区的差异。
基于观察到的Zucker（fa/fa）大鼠的骨骼表型，提示瘦素对骨骼有正向作用。
