[1]高飞,董旋,徐倩倩,等.AGEs对大鼠骨髓间充质干细胞成骨分化中β-catenin、ALP的影响及PTH的干预作用[J].国际内分泌代谢杂志,2021,41(03):173-177.[doi:10.3760/cma.j.cn121383-20210225-02059]
　Gao Fei,Dong Xuan,Xu Qianqian,et al.Effects of AGEs on β-catenin and ALP in osteogenic differentiation of rat bone marrow mesenchymal stem cells and the intervention of PTH[J].International Journal of Endocrinology and Metabolism,2021,41(03):173-177.[doi:10.3760/cma.j.cn121383-20210225-02059]
点击复制

AGEs对大鼠骨髓间充质干细胞成骨分化中β-catenin、ALP的影响及PTH的干预作用()
分享到：

《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
41
期数:
2021年03期
页码:
173-177
栏目:
论著
出版日期:
2021-05-20

文章信息/Info

Title:
Effects of AGEs on β-catenin and ALP in osteogenic differentiation of rat bone marrow mesenchymal stem cells and the intervention of PTH
作者:
高飞1; 董旋2; 徐倩倩1; 闫文楠1; 高虹1; 霍建忠3; 杨静1
1山西医科大学第一医院内分泌科,太原 030001; 2河北医科大学实验诊断学教研室,石家庄 050011; 3山西白求恩医院骨科,太原 030032
Author(s):
Gao Fei1;  Dong Xuan2;  Xu Qianqian1;  Yan Wennan1;  Gao Hong1;  Huo Jianzhong3;  Yang Jing1.
1Department of Endocrinology, The First Hospital of Shanxi Medical University, Taiyuan 030001, China; 2Department of Experimental Diagnostics, Hebei Medical University, Shijiazhuang 050011, China; 3Department of Orthopaedi
关键词:
晚期糖基化终末产物;  骨髓间充质干细胞;  β-catenin;  碱性磷酸酶;  甲状旁腺激素
Keywords:
Advanced glycation end products;  Bone marrow mesenchymal stem cells;  β-catenin;  Alkaline phosphatase;  Parathyroid hormone
DOI:
10.3760/cma.j.cn121383-20210225-02059
摘要:
目的 初步探讨在培养的骨髓间充质干细胞(BMSCs)层面,晚期糖基化终末产物(AGEs)对BMSCs成骨分化中β-catenin、碱性磷酸酶(ALP)的影响,以及甲状旁腺激素(PTH)的干预及其机制。方法 取第三代BMSCs,检测AGEs对其增殖的影响。将BMSCs分为对照组、AGEs组、Wnt3a组、AGEs+Wnt3a组; 对照组、AGEs组、AGEs+晚期糖基化终末产物受体(RAGE)抗体组; 对照组、AGEs组、AGEs+PTH组; 对照组、PTH组、PTH+Dickkopf相关蛋白1(DKK1)组,应用Western-blot法检测β-catenin、ALP蛋白的表达。结果 BMSCs的增殖可以被AGEs抑制。0.2 g/L AGEs干预BMSCs 7 d,AGEs抑制β-catenin、ALP蛋白表达有统计学差异; 给予Wnt通路促进剂Wnt3a后,AGEs作用被抑制,β-catenin、ALP蛋白表达较AGEs组增加; 加入10 mg/L RAGE中和抗体共培养,与AGEs组相比,β-catenin、ALP蛋白表达增高。加入PTH后可以逆转AGEs的负性成骨作用,β-catenin、ALP蛋白表达增高; 加入Wnt通路阻滞剂DKK1共培养,β-catenin、ALP蛋白表达较PTH组增加。结论 AGEs-RAGE通过Wnt/β-catenin信号通路抑制大鼠BMSCs ALP蛋白表达; PTH逆转AGEs对β-catenin、ALP的负性作用。
Abstract:
Objective To explore the effect of advanced glycation end products(AGEs)on β-catenin and alkaline phosphatase(ALP)in osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs), and the intervention of parathyroid hormone(PTH)and its mechanism in cultured BMSCs.Methods The third generation of BMSCs were taken to detect the effect of AGEs on their proliferation. BMSCs were divided into control group, AGEs group, Wnt3a group, AGEs+Wnt3a group; control group, AGEs group, AGEs+RAGE antibody group; control group, AGEs group, AGEs+PTH group; control group, PTH group, PTH+DKK1 group. The expression of β-catenin and ALP protein were detected by Western-blot.Results The proliferation of BMSCs was inhibited by AGEs. After 0.2 mg/ml AGEs treatment of BMSCs for 7 days, there was significant difference in the inhibition of β-catenin and ALP protein expression by AGEs; after administration of Wnt pathway promoter Wnt3a, the effect of AGEs was inhibited and the expression of β-catenin and ALP protein were increased compared with AGEs group; when co-cultured with 10 μg/ml RAGE neutralization antibody, the expression of β-catenin and ALP protein were increased compared with AGEs group. The negative osteogenic effect of AGEs was reversed and the expression of β-catenin and ALP protein were increased by adding PTH, and the expression of β-catenin and ALP protein in cells co-cultured with DKK1, a blocker of Wnt pathway, were higher than those in PTH group.Conclusion AGEs-RAGE inhibits the expression of ALP in rat BMSCs through Wnt/β-catenin signal pathway, and PTH reverses the negative effects of AGEs on β-catenin and ALP.

参考文献/References:

[1] Mercer N,Ahmed H,Etcheverry SB,et al.Regulation of advanced glycation end product(AGE)receptors and apoptosis by AGEs in mosteoblast—like cells[J].Mol Cell Biochem,2007,306(1-2):87-94.DOI:10.1007/s11010-007-9557-8.
[2] Li G,Xu J,Li Z.Receptor for advanced glycation end products inhibits proliferation in osteoblast through suppression of Wnt,PI3K and ERK signaling[J].Biochem Biophys Res Commun,2012,423(4):684-689.DOI:10.1016/j.bbrc.2012.06.015.
[3] Ott C,Jacobs K,Haucke E,et al.Role of advanced glycation end products in cellular signaling[J].Redox Biol,2014,2:411-429.DOI:10.1016/j.redox.2013.12.016.
[4] Okazaki K,Yamaguchi T,Tanaka K,et al.Advanced glycation end products(AGEs),but not high glucose,inhibit the osteoblastic differentiation of mouse stromal ST2 cells through the suppression of osterix expression,and inhibit cell growth and increasing cell apoptosis[J].Calcif Tissue Int,2012,91(4):286-296.DOI:10.1007/s00223-012-9641-2.
[5] Quarto N,Behr B,Longaker MT.Opposite spectrum of activity of canonical Wnt signaling in the osteogenic context of undifferentiated and differentiated mesenchymal cells:implications for tissue engineering[J].Tissue Eng Part A,2010,16(10):3185-3197.DOI:10.1089/ten.tea.2010.0133.
[6] 葛志敏,郭中豪,高飞.大鼠骨髓间充质干细胞的分离、培养与鉴定[J].中国临床研究,2015,28(7):836-839.DOI:10.13429/j.cnki.cjcr.2015.07.002.
[7] Asadipooya K,Uy EM.Advanced glycation end products(AGEs),receptor for AGEs,diabetes,and bone: review of the literature[J].J Endocr Soc,2019,3(10):1799-1818.DOI:10.1210/js.2019-00160.
[8] Aikawa E,Fujita R,Asai M,et al.Receptor for advanced glycation end products-mediated signaling impairs the maintenance of bone marrow mesenchymal stromal cells in diabetic model mice[J].Stem Cells Dev,2016,25(22):1721-1732.DOI:10.1089/scd.2016.0067.
[9] Wu L,Wei Q,Lv Y,et al.Wnt/β-catenin pathway is involved in cadmium-induced inhibition of osteoblast differentiation of bone marrow mesenchymal stem cells[J].Int J Mol Sci,2019,20(6):1519.DOI:10.3390/ijms20061519.
[10] Gong JH,Dong JY,Xie T,et al.The influence of AGEs environment on proliferation,apoptosis,homeostasis,and endothelial cell differentiation of human adipose stem cells[J].Int J Low Extrem Wounds,2017,16(2):94-103.DOI:10.1177/1534734617701575.
[11] Jiang M,Wang X,Wang P,et al.Inhibitor of RAGE and glucoseinduced inflammation in bone marrow mesenchymal stem cells:effect and mechanism of action[J].Mol Med Rep,2020,22(4):3255-3262.DOI:10.3892/mmr.2020.11422.
[12] Osagie-Clouard L,Sanghani-Kerai A,Coathup M,et al.The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats[J].Bone Joint Res,2019,8(8):397-404.DOI:10.1302/2046-3758.88.BJR-2019-0018.R1.
[13] Fan Y,Hanai JI,Le PT,et al.Parathyroid hormone directs bone marrow mesenchymal cell fate[J].Cell Metab,2017,25(3):661-672.DOI:10.1016/j.cmet.2017.01.001.
[14] Ohishi M,Schipani E.PTH and stem cell[J].J Endocrinol Invest,2011,34(7):552-556.DOI:10.3275/7620.

相似文献/References:

[1]闫淑芳,杜少斐,吴敬,等.高糖在联合转录因子诱导大鼠骨髓间充质 干细胞分化为胰岛样细胞中的作用[J].国际内分泌代谢杂志,2017,37(02):77.[doi:10.3760/cma.j.issn.1673-4157.2017.02.002]
　Yan Shufang*,Du Shaofei,Wu Jing,et al.Effects of high glucose on the differentiation of rat bone marrow mesenchymal stem cells into insulin-producing cells induced by transcriptional factors[J].International Journal of Endocrinology and Metabolism,2017,37(03):77.[doi:10.3760/cma.j.issn.1673-4157.2017.02.002]
[2]李博,苏青.晚期糖基化终末产物及其受体与非酒精性脂肪性肝病的 关系[J].国际内分泌代谢杂志,2017,37(03):192.[doi:10.3760/cma.j.issn.1673-4157.2017.03.013]
　Li Bo,Su Qing..Relationship between advanced glycation end-products and its receptor in nonalcoholic fatty liver diseases[J].International Journal of Endocrinology and Metabolism,2017,37(03):192.[doi:10.3760/cma.j.issn.1673-4157.2017.03.013]
[3]符灵芝,刘鸿飞,谢芬,等.外泌体在骨代谢中的作用[J].国际内分泌代谢杂志,2017,37(05):316.
　Fu Lingzhi,Liu Hongfei,Xie Fen,et al.Role of exosomes in bone metabolism[J].International Journal of Endocrinology and Metabolism,2017,37(03):316.
[4]高四书 王龙 华飞.晚期糖基化终末产物与多囊卵巢综合征的关系[J].国际内分泌代谢杂志,2018,38(04):279.[doi:10.3760/cma.j.issn.1673-4157.2018.04.015]
　Gao Sishu,Wang Long,Hua Fei.Relationship between advanced glycation end-products and polycystic ovary syndrome[J].International Journal of Endocrinology and Metabolism,2018,38(03):279.[doi:10.3760/cma.j.issn.1673-4157.2018.04.015]
[5]何沙沙,张洁,管璐璐,等.食源性晚期糖基化终末产物对肠道菌群及代谢相关疾病的影响研究进展[J].国际内分泌代谢杂志,2023,43(01):10.[doi:10.3760/cma.j.cn121383-20220131-01060]
　He Shasha,Zhang Jie,Guan Lulu,et al.Research progress on the effects of dietary advanced glycation end products on intestinal flora and metabolic disease[J].International Journal of Endocrinology and Metabolism,2023,43(03):10.[doi:10.3760/cma.j.cn121383-20220131-01060]

备注/Memo

备注/Memo:
通信作者:杨静,Email:yangjlm@126.com
更新日期/Last Update: 2021-05-20