去卵巢骨质疏松大鼠成骨细胞G_1期调节蛋白的改变  

Changes in G_1 phase regulatory protein of osteoblasts in ovariectomized osteoporosis rats

作　　者：吴银生[1] 林燕萍[1] 卢天祥[2] 林煜[1] 黄云梅[3] 黄美雅[3] 

机构地区：[1]福建中医学院中西医结合研究院骨病研究所,福建省福州市350108 [2]福建省泉州市第一医院骨科,福建省泉州市362000 [3]福建中医学院中西医结合研究院基础重点实验室,福建省福州市350108

出　　处：《中国组织工程研究与临床康复》2010年第15期2675-2679,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：国家自然科学基金项目(30572402);福建省科技厅社发处重点项目(2009Y0028);福建省科技厅青年人才项目(2008F3054);福建省中西医结合老年性疾病重点实验室(福建中医学院)开放课题·陈可冀中西医结合发展基金资助项目(2008J1004-30、CKJ2008067)的资助~~

摘　　要：背景:G1期调节蛋白对调控增殖细胞的增殖周期具有重要作用,目前关于成骨细胞G1期调节蛋白的研究甚少,绝经后骨质疏松与成骨细胞G1期调节蛋白的关系更未被阐明。目的:观察去卵巢大鼠骨质疏松发病过程中成骨细胞G1期调节蛋白的改变,探讨绝经后骨质疏松症的发病机制。方法:100只6月龄SD雌性大鼠,随机分成假手术组和模型组各50只,模型组进行双侧卵巢结扎切除术,假手术组除未行卵巢结扎切除外,其余步骤与手术组相同。所有大鼠于术后4,8,12,18,24周分批取材,每批每组各处死10只,取大鼠腰椎。运用免疫组织化学方法检测骨组织中成骨细胞G1期调节蛋白CyclinD1、CDK4、p21蛋白表达。结果与结论:CyclinD1、CDK4蛋白阳性表达主要定位于骨小梁表面的成骨细胞。假手术组有CyclinD1、CDK4蛋白阳性表达,模型组表达强于假手术组。p21蛋白阳性表达部位与CyclinD1相似,假手术组和模型组均有明显阳性表达,但模型组的表达维持在较高水平,在各时期均明显高于同期假手术组(P<0.01)。结果证实,去卵巢骨质疏松模型大鼠发病过程中,成骨细胞CyclinD1、CDK4、p21蛋白出现明显高表达。提示成骨细胞增殖加快,同时成骨细胞周期受阻滞亦增多,成骨细胞数量相对不足,骨形成低于骨吸收,导致骨质疏松的发生。BACKGROUND：G1 phase regulatory protein plays an important role in regulating cell reproductive cycle.However,there are few reports concerning research of G1 phase regulatory protein of osteoblasts,and the relationship between postmenopausal osteoporosis and the G1 phase regulatory protein of osteoblasts have not been explained.OBJECTIVE：To observe the change of G1 phase regulatory protein of osteoblasts in the ovariectomized osteoporosis rats,and to investigate the pathogenesis of postmenopausal osteoporosis.METHODS：Totally 100 6-month-old SD female rats were randomly divided into sham surgery and model groups,with 50 animals in each group.Rats in the model group were performed bilaterally ovariectomy,those in the sham surgery group were subjected to sham surgery.Ten rats of each group were sacrificed at 4,8,12,18 and 24 weeks after operation,respectively.The expression of Cyclin D1,CDK4,and p21 protein in osteoblasts of lumbar vertebra were measured by immunohistochemistry.RESULTS AND CONCLUSION：Cyclin D1 and CDK4-positive expression mainly located at osteoblasts which in the superficies of bone trabecula.There was Cyclin D1 and CDK4 positive expression in the sham surgery group,but was obviously smaller than that of the model group.The location of p21 positive expression was similar to Cyclin D1.Obviously positive expression of p21 appeared in the bone tissue of both groups,in which that of the model group maintained at a high level,and higher than that of the sham surgery group at different periods after operation（P〈0.01）.The results demonstrated that Cyclin D1,CDK4 and p21 in osteoblasts were hyper-expressed in the process of osteoporosis in ovariectomized rats.It suggested that faster osteoblast proliferation and inhabited osteoblast cell cycles result in relative insufficiency of osteoblast,thus the bone formation is smaller than bone resorption,eventually,lead to the occurrence of osteoporosis.

关 键 词：绝经后骨质疏松症 细胞周期蛋白D1 细胞周期蛋白质依赖激酶 癌基因蛋白质P21 骨组织工程 

分 类 号：R318[医药卫生—生物医学工程]