依降钙素干预膝骨关节炎模型大鼠软骨下骨的变化  

Changes of subchondral bone in rat models of knee osteoarthritis treated by elcatonin

作　　者：伍琦[1,2] 廖瑛[1,2] 孙光华[1,2] 周桂娟[1,2] 廖源[1,2] 刘静 钟培瑞 成果 邓程远 王甜甜 Wu Qi;Liao Ying;Sun Guanghua;Zhou Guijuan;Liao Yuan;Liu Jing;Zhong Peirui;Cheng Guo;Deng Chengyuan;Wang Tiantian(Department of Rehabilitation Medicine,the First Affiliated Hospital of University of South China,Hengyang 421001,Hunan Province,China;Rehabilitation Laboratory,the First Affiliated Hospital of University of South China,Hengyang 421001,Hunan Province,China;University of South China,Hengyang 421001,Hunan Province,China)

机构地区：[1]南华大学附属第一医院康复医学科,湖南省衡阳市421001 [2]南华大学附属第一医院康复医学实验室,湖南省衡阳市421001 [3]南华大学,湖南省衡阳市421001

出　　处：《中国组织工程研究》2020年第5期709-715,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(81674045)，项目负责人：廖瑛;湖南省自然科学基金青年基金项目(S2019JJ50536)，项目负责人：伍琦~~

摘　　要：背景:骨关节炎存在软骨下骨吸收和骨形成失去平衡,课题组前期研究发现膝骨关节炎大鼠关节软骨改变前软骨下骨就已经发生改变。目的:通过观察膝骨关节炎大鼠膝关节软骨下骨的变化,探讨依降钙素对软骨下骨p38 MAPK表达及软骨下骨吸收的影响。方法:雌性3月龄SD大鼠随机分为3组:假手术组(n=6)不切除卵巢,切除同卵巢等体积大小的脂肪组织,切开双侧膝关节,但不损伤交叉韧带;模型组(n=6)切除双侧卵巢后,再切断双侧膝关节前交叉韧带,建立卵巢切除+前交叉韧带切断模型,不进行药物干预;依降钙素组(n=6)建立卵巢切除+前交叉韧带切断模型后,依降钙素5 IU/kg,每周2次肌肉注射。12周后分析软骨下骨的骨密度、软骨下骨p38蛋白表达水平以及血清Ⅰ型胶原交联C-末端肽、Ⅱ型胶原交联C-末端肽、白细胞介素1、白细胞介素6、骨特异性碱性磷酸酶、抗酒石酸酸性磷酸酶5b水平。实验方案经南华大学动物实验伦理委员会批准。结果与结论:(1)依降钙素组软骨下骨的骨体积分数、骨小梁数量显著高于模型组(P<0.05),骨小梁分离度显著低于模型组(P<0.05);(2)模型组的骨体积分数、骨小梁数量、骨小梁厚度显著低于假手术组(P<0.01或<0.05)、骨小梁分离度显著高于假手术组(P<0.01);(3)依降钙素组血清Ⅰ型胶原交联C-末端肽、白细胞介素1、白细胞介素6、抗酒石酸酸性磷酸酶5b显著低于模型组(P<0.05),模型组Ⅰ型胶原交联C-末端肽、Ⅱ型胶原交联C-末端肽、白细胞介素1、白细胞介素6、抗酒石酸酸性磷酸酶5b明显高于假手术组(P<0.05);(4)软骨下骨p38蛋白表达水平依降钙素组显著低于模型组(P<0.01)、模型组显著高于假手术组(P<0.01);(5)结果说明,依降钙素可能通过下调p38MAPK表达,抑制骨关节炎促炎因子分泌及软骨下骨吸收。BACKGROUND:Imbalance between subchondral bone resorption and bone formation occurs in osteoarthritis.Our preliminary study has found that the subchondral bone changes precede the articular cartilage changes in knee osteoarthritis rats.OBJECTIVE:To observe the changes of subchondral bone in knee osteoarthritis rats,and to explore the effect of elcatonin on the expression of p38 MAPK and absorption of subchondral bone.METHODS:Female Sprague-Dawley rats,3 months of age,were randomly divided into three groups:sham operation group(n=6,the adipose tissue of the same size as the ovary was removed without ovariectomy,the bilateral knee joints were opened,but without cruciate ligament injury);model group(n=6,bilateral ovariectomy plus bilateral cruciate ligament injury,no treatment);elcatonin group(n=6,ovariectomy plus cruciate ligament injury,intramuscular injection of 5 IU/kg elcatonin,twice weekly).The bone mineral density and p38 protein expression levels in subchondral bone were detected at 12 weeks.The serum levels of C-terminal crosslinking telopeptides of type I collagen,C-terminal crosslinking telopeptides of type Ⅱ collagen,interleukin-1,interleukin-6 and bone-specific alkaline phosphatase,tartrate resistant acid phosphatase 5 b were detected.RESULTS AND CONCLUSION:(1) The bone volume fraction and trabecular bone number in the elcatonin group were significantly higher than those in the model group(P <0.05),and the trabecular separation in the elcatonin group was lower than that in the model group(P <0.05).(2) The bone volume fraction,trabecular bone number and trabecular thickness in the model group were lower than those in the sham operation group(P<0.01 or P<0.05),and the trabecular separation was higher than that in the sham operation group(P<0.01).(3) The serum levels of C-terminal crosslinking telopeptides of type I collagen,C-terminal crosslinking telopeptides of type Ⅱ collagen,interleukin-1,interleukin-6 and tartrate resistant acid phosphatase 5 b in the elcatonin group was significantly lower than t

关 键 词：骨关节炎 依降钙素 软骨下骨 骨吸收 p38 MAPK 骨组织定量 促炎症因子 抗酒石酸酸性磷酸酶5B 骨特异性碱性磷酸酶 Ⅰ型胶原交联C-末端肽 Ⅱ型胶原交联C-末端肽 

分 类 号：R446[医药卫生—诊断学] R496[医药卫生—临床医学]