四连接素基因敲除小鼠表现出脊柱后凸畸形和骨质疏松症的特征  

Tetranectin knock-out mice exhibit features of kyphosis and osteoporosis

作　　者：茹德文 颜玉峰[1] 李炳[2] 谢强[1] 汤日 沈晓[1] 余果[1] 杜嘉瑞[1] 王尔松[1] 

机构地区：[1]复旦大学附属金山医院神经外科,上海201508 [2]复旦大学附属金山医院中心实验室,上海201508

出　　处：《复旦学报（医学版）》2016年第2期159-163,169,共6页Fudan University Journal of Medical Sciences

基　　金：上海市科学技术委员会基金(124119a1900);上海市卫生和计划生育委员会基金(20124339)~~

摘　　要：目的研究四连接素(tetranectin,TN)基因敲除对小鼠骨骼生长发育的影响,从而探究该基因的正常生理功能及其缺失与疾病的关系。方法通过基因同源重组的方法构建出TN基因敲除(TN^(-/-))小鼠模型,分别对2月龄和8月龄的TN^(-/-)雄性小鼠(n=10)和同龄野生型(wild-type,WT)雄性小鼠(n=10)进行全身正侧位X线摄片和脊柱后凸角度(Cobb角)测量,并对8月龄TN^(-/-)雄性小鼠(n=10)和WT雄性小鼠(n=10)的多部位骨骼进行骨密度(bone mineral density,BMD)及骨矿含量(bone mineral content,BMC)测定和病理切片检查,所得数据进行统计学分析。结果TN^(-/-)小鼠与同龄WT小鼠体质量无明显差异;2月龄及8月龄TN^(-/-)小鼠Cobb角均较同龄WT小鼠显著增大(P<0.01),且随月龄增加,Cobb角显著增大(P<0.01);8月龄TN^(-/-)小鼠的胸椎椎间盘结构不对称,外侧纤维环呈增大、疏松改变;与同龄WT小鼠相比,8月龄TN^(-/-)小鼠全身、腰3椎体和左侧股骨BMD及BMC显著降低(P<0.05),股骨及腰椎在组织学上也呈现出骨小梁变细、稀疏、排列紊乱或断裂等特点,且骨小梁成骨细胞减少,破骨细胞增多。结论TN^(-/-)小鼠表现出脊柱后凸畸形和骨质疏松症的特征,提示TN与骨骼的正常生长发育关系密切。TN^(-/-)小鼠作为一种潜在的脊柱后凸畸形或骨质疏松症疾病动物模型具有重大的研究意义。Objective To investigate the effect of tetranectin（TN）deletion on mice skeleton growth and development,and to explore the physiological function of TN gene and the relationship between its deletion and diseases. Methods TN gene knock-out（TN^（-/-））mice were generated by the method of gene homologous recombination.In two-month-old and eight-month-old TN^（-/-）mice,X-ray radiography of whole body anteroposterior and lateral position were carried out,and the angle of kyphosis（namely Cobb＇s angle） was detected,respectively,as well as their wild-type（WT）littermates.Moreover, bone mineral density（BMD）, bone mineral content（BMC）, and pathological sections of multisite were examined in eight-month-old TN^（-/-）mice and their WT littermates. Results Body weight between TN^（-/-）mice and their WT littermates showed no significant difference.Cobb＇s angle of both two-month-old and eight-month-old TN^（-/-）mice increased significantly compared with their littermates（P0.01）.Cobb＇s angle increased significantly with age in TN^（-/-）mice（P0.01）.Asymmetric thoracic intervertebral disc structure and expanded and loose fibrous ring of intervertebral disc were distinct in TN^（-/-）mice.Compared with their WT littermates,eight-month-old TN^（-/-）mice demonstrated a significant decrease of BMD and BMC in the whole body,third lumbar vertebra and left femur（P0.05）.Besides,it was observed that TN^（-/-）mice exhibited characteristics of thinner,sparse,and disordered arrangement or rupture of femur and lumbar vertebras bone trabecula with decreased osteoblasts and increased osteoclasts. Conclusions TN^（-/-）mice exhibit features of kyphosis and osteoporosis,which suggests that there is a close relationship between tetranectin and the normal growth and development of skeleton.TN^（-/-）mice may be a potential animal model for kyphosis or osteoporosis and deserves further study.

关 键 词：四连接素 基因敲除 脊柱后凸畸形 骨质疏松症 小鼠 

分 类 号：R682.2[医药卫生—骨科学]