[1]贾祎佳,罗春山,陆廷盛,等. 音猬因子修饰的骨髓间充质干细胞治疗大鼠骨质疏松的实验研究[J].中华老年骨科与康复电子杂志,2019,(04):211-216.[doi:DOI:10.3877/cma.j.issn.2096-0263.2019.04.006]
 Jia Yijia,Luo Chunshan,Lu Tingsheng,et al. Effect of bone marrow stromal cells transferred with sonic hedgehog gene on osteoporosis in ovariectomized rats[J].Chin J Geriatr Orthop Rehabil(Electronic Edition),2019,(04):211-216.[doi:DOI:10.3877/cma.j.issn.2096-0263.2019.04.006]
点击复制

 音猬因子修饰的骨髓间充质干细胞治疗大鼠骨质疏松的实验研究
()
分享到:

中华老年骨科与康复电子杂志[ISSN:1674-3911/CN:11-9292/R]

卷:
期数:
2019年04期
页码:
211-216
栏目:
论著
出版日期:
2019-08-05

文章信息/Info

Title:
 Effect of bone marrow stromal cells transferred with sonic hedgehog gene on osteoporosis in ovariectomized rats
作者:
 贾祎佳 罗春山 陆廷盛 姚书眈 蒲兴魏 杨建文 陈啟鸰

作者单位:550002 贵阳,贵州省骨科医院脊柱外科
Author(s):
 Jia YijiaLuo ChunshanLu Tingsheng Yao ShudanPu XingweiYang Jianwen Chen Qiling.
 Department of spine surgery, Guizhou Province Osteological Hospital, Guiyang 550002, China
关键词:
 【关键词】 间充质干细胞 音猬因子蛋白大鼠 骨质疏松 细胞移植
Keywords:
 【Key words】 Marrow stromal cells Sonic hedgehog protein rat Osteoporosis Cell transplantaion
DOI:
DOI:10.3877/cma.j.issn.2096-0263.2019.04.006
文献标志码:
A
摘要:
 【摘要】 目的 探讨转染音猬因子的骨髓间充值干细胞移植对卵巢切除骨质疏松大鼠的治疗作用。方法 选取40只雌性SD大鼠,分为假手术组、模型组、骨髓间充值干细胞(BMSCs)移植组和音猬因子修饰的骨髓间充值干细胞(Shh-BMSCs)移植组,每组10只动物。假手术组手术中仅摘除卵巢附近的脂肪组织,但不摘除卵巢。其余的3组均进行双侧的卵巢切除手术,建立骨质疏松模型,在骨质疏松造模后的2个月,BMSCs移植组和Shh-BMSCs移植组分别通过大鼠的尾静脉注射BMSCs与Shh-BMSCs(第四代,约2*106个干细胞),模型组动物注射等量PBS液体。在干细胞移植2 w后,检测尾静脉中血清钙、磷、碱性磷酸酶水平,同时采用双能X射线骨密度仪测量大鼠的股骨、腰椎及全身骨密度,micro-CT扫描进行胫骨的形态计量学指标分析。结果 (1)与假手术组相比,模型组的大鼠骨小梁厚度、骨小梁数量和骨体积分数均明显减少,大鼠的骨密度、血清钙与碱性磷酸酶明显降低,而大鼠的血清磷水平明显升高,差异有统计学意义(P<0.05),以上表明骨质疏松大鼠模型成功制备。(2)与模型组相比,BMSCs组的大鼠血清钙和和碱性磷酸酶明显升高,而血清磷水平明显降低,差异有统计学意义(P<0.05)。与模型组、BMSCs组相比,Shh-BMSCs组大鼠血清钙、碱性磷酸酶水平明显升高,而血清磷水平明显降低,差异有统计学意义(P<0.05)。(3)同模型组的骨密度相比,BMSCs组大鼠的骨密度明显升高,差异有统计学意义(P<0.05);与模型组、BMSCs组相比,Shh-BMSCs组大鼠的骨密度明显升高,差异有统计学意义(P<0.05)。(4)同模型组相比,BMSCs组的大鼠骨小梁厚度、骨小梁数量和骨体积分数均明显增加,差异有统计学意义(P<0.05),与模型组和BMSCs组相比,Shh-BMSCs组的大鼠骨小梁厚度、骨小梁数量和骨体积分数均明显增加,差异有统计学意义(P<0.05)。结论 Shh-BMSCs细胞移植后能够治疗大鼠卵巢切除后的骨质疏松。
Abstract:
 
【Abstract】 Objective To research the effect of bone marrow stromal cells transferred with sonic hedgehog gene (Shh-BMSCs) transplantation about osteoporosis in ovariectomized rats. Methods Forty female SD rats were divided into control group, model group, bone marrow stem cells (BMSCs) transplantation group and bone marrow stromal cells transferred with sonic hedgehog gene (Shh-MSCs) transplantation group, each group has ten animals. Rats in control group were only removed adipose tissue around the ovaries, not their ovaries. The rest of the three groups were performed bilateral ovariectomy, and osteoporosis model was established. Two months after modeling, rats in the BMSCs or Shh-BMSCs transplantation group were respectively given BMSCs or Shh-BM SCs via the rat tail intravenous (fourth generation, about 2*106 stem cells), and the same amount of PBS was injected in the model group. Two weeks after treatment, levels of serum calcium, phosphorus, alkaline phosphatase were detected in rats, and bone mineral density was measured using dual energy X-ray, at the same timetibial form metrology was analyzed by micro -CT scan. Results (1) Compared with the control group, the bone trabecular thickness, trabecular bone quantity and bone volume fraction were significantly decreased in the model group (P<0.05). There was a significant reduction in the bone mineral density of the rat femur, lumbar spine and whole body as well as the levels of serum calcium and alkaline phosphatase, however the phosphorus was increased significantly (P<0.05).These findings indicate the successful preparation of the ostesporosis rat model. (2) Compared with the ovariedomized group,the levels of serum calcium and alkaline phosphatase were significantly higher in the BMSCs group,however the phosphorus was decreased significantly (P<0.05). Compared with the ovariedomized and BMSCs groups,the levels of serum calcium and alkaline phosphatase were significantly higher in the Shh-BMSCs group,however the phosphorus was decreased significantly (P<0.05). (3) Compared with the ovariedomized group,the bone mineral density of the rat femur, lumbar spine or whole body was significantly higher in the BMSCs group(P<0.05). Compared with the ovariedomized and BMSCs groups, the bone mineral density of the rat femur, lumbar spine or whole body was significantly higher in the Shh-BMSCs group(P<0.05). (4) Compared with the ovariedomized group,the number and thickness of trabeculae and bone volume fraclio was significantly higher in the BMSCs group(P<0.05). Compared with the ovariedomized and BMSCs groups,the number and thickness of trabeculae and bone volume fraclio was significantly higher in the Shh-BMSCs group(P<0.05). Conclusion Shh-BMSCs exerts therapeutic effects on osteoporosis in ovariectomized rats.

参考文献/References:

 1 刘忠厚. 骨质疏松学 [M] . 北京: 科学出版社, 1998: 529.
2 Honig S. Osteoporosis - new treatments and updates [J]. Bull NYU Hosp Jt Dis, 2010, 68(3): 166-170.
3 Papanicolaou DA, Wilder RL, Manolagas SC, et al. The pathophysiologic roles of interleukin-6 in human disease [J]. Ann Intern Med, 1998, 128(2): 127-137.
4 罗南萍, 刘恒国. 骨质疏松症与相关细胞因子的研究 [J]. 放射免疫学杂志, 2007, 20(2): 132-136.
5 盛柩, 谢培凤, 王新祥. 原发性骨质疏松症从脾论治及相关机制探讨 [J]. 中华中医药杂志, 2012, 27(7): 1922-1926.
6 Vural P, Akgul C, Canbaz M. Effects of hormone replacement therapy on plasma pro-inflammatory and anti-inflammatory cytokines and some bone turnover markers in postmenopausal women [J]. Pharmacol Res, 2006, 54(4): 298-302.
7 Uemura H, Kamada M, Maegawa M, et al. Effect of hormone replacement therapy on the production of bone-resorbing cytokines by peripheral blood cells in postmenopausal women [J]. Horm Metab Res, 2005, 37(4): 226-230.
8 Eriksson PS, Perfilieva E, Björk-Eriksson T, et al. Neurogenesis in the adult human hippocampus [J]. Nat Med, 1998, 4(11): 1313-1317.
9 张晓玲, 戴尅戎, 汤亭亭, 等. 未分化骨髓间充质干细胞的免疫学特性研究 [J]. 中华实验外科杂志, 2006, 23(2): 135-137.
10 Ma XL, Zhang XE, Jia YF, et al. Dexamethasone induces osteogenesis via regulation of hedgehog signalling molecules in rat mesenchymal stem cells [J]. Int Orthop, 2013, 37(7): 1399-1404.
11 Zhang XS, Linkhart TA, Chen ST, et al. Local ex vivo gene therapy with bone marrow stromal cells expressing human BMP4 promotes endosteal bone formation in mice [J]. J Gene Med, 2004, 6(1): 4-15.
12 Zimmermann S, Voss M, Kaiser S, et al. Lack of telomerase activity in human mesenchymal stem cells [J]. Leukemia, 2003, 17(6): 1146-1149.
13 Simonsen JL, Rosada C, Serakinci N, et al. Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells [J]. Nat Biotechnol, 2002, 20(6): 592-596.
14 Zhao YM, Li JY, Lan JP, et al. Cell cycle dependent telomere regulation by telomerase in human bone marrow mesenchymal stem cells [J]. Biochem Biophys Res Commun, 2008, 369(4): 1114-1119.
15 Bunnell BA, Estes BT, Guilak F, et al. Differentiation of adipose stem cells [J]. Methods Mol Biol, 2008,456:155-171
16 张颖, 张博, 张治国, 等. 从肝脾肾三脏探讨绝经后骨质疏松症的发病机理 [J]. 中国中医基础医学杂志, 2012, 18(1): 36-42.
17 李雪琳. 中西医结合治疗绝经妇女骨质疏松症30例 [J]. 实用中医药杂志, 2012, 28(4): 285-286.
18 Kimura H1, Ng JM, Curran T. Transient inhibitiion of the hedgehog pathway in young mice causes permanent defects in bone structure [J]. Cancer Cell, 2008, 13(3): 1-46.
19 Blank U, Karlsson G, Karlsson S. Signaling pathways governing stem-cell fate [J]. Blood, 2008, 111(2): 249-260.
20 Stucki U, Schmid J, Hammerle CF, et al. Temporal and local appearance of alkaline phosphatase activity in early stages of guided bone regeneration [J]. Clin Oral Implants Res, 2001, 12(2):121-127.
21 Peng Z, Tuukkanen J, Väänänen HK. Exercise can provide protection against bone loss and prevent the decrease in mechanical strength of femoral neck in ovariectomized rats [J]. J Bone Miner Res, 1994, 9(10): 1559-1564.

相似文献/References:

[1]鲍飞龙 刘涛 亢世杰 黄东生 江涛 胡义明. 双反牵引装置治疗Schatzker分型Ⅴ、Ⅵ型胫骨平台骨折的优势[J].中华老年骨科与康复电子杂志,2018,(05):266.
 Bao Feilong,Liu Tao,Kang Shijie,et al.The advantage of homeopathic double reverse traction device treating tibial plateau fractures of typing Schatzker Ⅴ and Ⅵ[J].Chin J Geriatr Orthop Rehabil(Electronic Edition),2018,(04):266.
[2]王哲培 张凯 保罗 汪毅 白震民. 太极拳对老年女性下肢静态平衡、本体感觉与功能活动的影响[J].中华老年骨科与康复电子杂志,2018,(05):296.
 Wang Zhepei,Zhang Kai,Pablo,et al. The influence of Taijiquan on the lower limbs static balance, proprioception and functional activities of older women[J].Chin J Geriatr Orthop Rehabil(Electronic Edition),2018,(04):296.
[3]刘磊 王宝泉 孙然 杨宗酉 孙家元 陈伟 王海立 殷兵 刘松 李石伦 杨光 张英泽. 2010年至2011年中国东部和西部地区成人股骨转子间骨折流行病学对比分析[J].中华老年骨科与康复电子杂志,2018,(05):302.
 Liu Lei,Wang Baoquan,Sun Ran,et al.Epidemiological comparison of adult femoral intertrochanteric fractures between the east and west areas in China from 2010 through 2011[J].Chin J Geriatr Orthop Rehabil(Electronic Edition),2018,(04):302.
[4]吴石磊 刘勇 邵增务 田青. 骨组织细胞外泌体对骨代谢作用的研究现状[J].中华老年骨科与康复电子杂志,2018,(05):308.
 Wu Shilei,Liu Yong,Shao Zengwu,et al. Research status of bone tissue-derived exosomes on bone metabolism[J].Chin J Geriatr Orthop Rehabil(Electronic Edition),2018,(04):308.
[5]张世峰 金群华. 胫骨高位截骨术治疗膝内侧单间室骨关节炎的研究进展[J].中华老年骨科与康复电子杂志,2018,(05):312.
 Zhang Shifeng,Jin Qunhua.. Research progress of high tibial osteotomy in the treatment of medial single compartment osteoarthritis[J].Chin J Geriatr Orthop Rehabil(Electronic Edition),2018,(04):312.
[6]赵永辉,陆声,马宇龙,等. 皮质骨通道螺钉技术在腰椎退变性疾病中的临床应用[J].中华老年骨科与康复电子杂志,2019,(03):123.[doi:10.3877/cma.j.issn.2096-0263.2019.001]
 Zhao Yonghui,Lu Sheng,Ma Yulong,et al. Clinical application of cortical bone screw technique in elderly patients with lumbar degenerative diseases[J].Chin J Geriatr Orthop Rehabil(Electronic Edition),2019,(04):123.[doi:10.3877/cma.j.issn.2096-0263.2019.001]
[7]王虎 李明 靳泽岳 连晓东 陈伟. 不同方法治疗老年股骨转子间合并转子下骨折的比较[J].中华老年骨科与康复电子杂志,2019,(03):135.[doi:DOI:10.3877/cma.j.issn.2096-0263.2019.003]
 Wang Hu,Chen Wei.. Comparative of different methods for the treatment of intertrochanteric-subtrochanteric fracture[J].Chin J Geriatr Orthop Rehabil(Electronic Edition),2019,(04):135.[doi:DOI:10.3877/cma.j.issn.2096-0263.2019.003]
[8]明立功 孟维娜 明朝戈 栗贡策 王自方 王新德 明立山 许振华.腓骨近端截骨联合中医药治疗膝关节内侧间室骨关节炎肝肾不足、气滞血瘀证[J].中华老年骨科与康复电子杂志,2019,(03):149.[doi:DOI:10.3877/cma.j.issn.2096-0263.2019.005]
 Ming Ligong,Meng Weina,Ming Chaoge,et al. Proximal fibular osteotomy combined with traditional Chinese medicine in the treatment of osteoarthritis of medial compartment of knee joint with liver and kidney insufficiency, qi stagnation and blood stasis syndrome[J].Chin J Geriatr Orthop Rehabil(Electronic Edition),2019,(04):149.[doi:DOI:10.3877/cma.j.issn.2096-0263.2019.005]
[9]胡建平 李俊峰 秦鸿雁 张强 张卫国 陈明. 长短髓内钉治疗老年股骨反转子间骨折的疗效比较[J].中华老年骨科与康复电子杂志,2019,(03):143.[doi:DOI:10.3877/cma.j.issn.2096-0263.2019.004]
 Hu Jianping,Li Junfeng,Qin Hongyan,et al. Comparison of short intramedullary nail and long intramedullary nail for the treatment of reverse oblique intertrochanteric fractures in the elderly[J].Chin J Geriatr Orthop Rehabil(Electronic Edition),2019,(04):143.[doi:DOI:10.3877/cma.j.issn.2096-0263.2019.004]
[10]魏宁 常文利 杜晨光 侯志勇 张世强 焦振清 李增炎 陈伟 张英泽. 河北医科大学第三医院956例后踝骨折的流行病学分析[J].中华老年骨科与康复电子杂志,2019,(03):167.[doi:DOI:10.3877/cma.j.issn.2096-0263.2019.008]
 Wei Ning,Chang Wenli,Du Chenguang,et al. The retrospective analysis of 956 cases with posterior malleolar fractures[J].Chin J Geriatr Orthop Rehabil(Electronic Edition),2019,(04):167.[doi:DOI:10.3877/cma.j.issn.2096-0263.2019.008]

备注/Memo

备注/Memo:

基金项目:贵州省卫生计生委科学技术基金项目(gzwjkj2016-1-029)
更新日期/Last Update: 2019-09-19