骨保护素基因敲除小鼠发生骨质疏松症的特征

Preliminary baseline observation of osteoporosis on osteoprotegerin-deficient mice

目的研究我国自行开发的骨保护素(OPG)基因敲除小鼠的骨质疏松基本数据及其所属的骨质疏松类型,为其进一步推广应用提供基线数据。方法将野生型OPG(OPG-WT)小鼠,7和13周龄的骨保护素基因敲除小鼠(OPG-/-)分成3组(每组6只),分别检测其血清碱性磷酸酶(ALP)、酸性磷酸酶(ACP)及骨钙素(OC)水平,并行骨密度测定、X线摄片、扫描电镜检查和生物力学测试,将所得数据进行统计学分析。结果OPG-/-小鼠的骨密度、股骨刚度和最大折断负荷均显著降低(P<0．01),血清ALP和ACP明显升高(P< 0．01),OC在早期与对照组无明显差异。OPG-/-小鼠在X线平片上表现为骨量减少,骨小梁稀疏或塌陷,骨皮质变薄。扫描电镜观察到OPG-/-小鼠骨小梁变细、变尖,骨小梁间隙增大,部分骨小梁塌陷。结论OPG-/-小鼠骨吸收活性增强伴继发性成骨活性提高,符合高转换型骨质疏松的特征,具有明显的优点,为研究OPG／OPGL／RANK体系提供了新的平台,有可能成为一种新的模型用于高转换型骨质疏松症的实验研究。

Purpose To investigate the preliminary baseline data of osteoporosis on osteoprotegerin （OPG）-deficient mice. Methods Three groups of mice were included, i. e. ,OPG^-WT group （as a control）, 7-week-old OPG gene knockout（OPG^-/ - ） group and 13-week-old OPG ^-/- group. Assessed parameters included serum alkaline phosphatase （ALP）, acid phosphatase （ACP） and osteocalcin （OC）, whole- body- radiography; BMD, biomechanical property of femurs; scan electron microscope was employed to observe the shape of lumbar vertebral trabecula. Results Compared with the control group, the level of serum ALP, ACP in both OPG^-/ - groups were significantly increased（P〈 0.01）, BMD, stiffness and strength of the femurs in OPG^-/ - groups were markedly decreased（P〈 0.01）. There was no significant difference in serum OC between the control group and 7-week-old OPG^-/ - group. Bone mass loss, cortical bone thinning, trabecular bone porosity and collapse were all found in radiographs of OPG^-/ - groups. Scan electron microscope showed that the vertebral trabeculae of OPG^-/ - groups were thin and discontinuous, with expanded trabecular space and partial collapse of trabeculae. Conclusions The osseous changes observed in OPG^-/ - mice are consistent with the characters of high - turnover osteoporosis, demonstrating a boost-up of bone resorption activity with secondary enhancement of bone formation, The OPG-mice may become a novel and-encouraging animal model for high turn-over osteoporosis, as well as for the study of the mechanisms of OPG/OPGL/ RANK system.