«上一篇/Previous Article|本期目录/Table of Contents|下一篇/Next Article»

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

28卷

期数:

2022年04期

页码:

378-382

栏目:

基础医学

出版日期:

2022-07-20

文章信息/Info

Title:

BMPER alleviates suppression of osteogenic differentiation by high glucose and high lipid in MC3T3-E1 cells via Wnt/β-catenin signaling pathway

文章编号:

1006-8147（2022）04-0378-05

作者:

刘峥; 谢云

（天津医科大学朱宪彝纪念医院老年病科，天津市内分泌研究所，国家卫生健康委员会激素与发育重点实验室，天津市代谢性疾病重点实验室，天津300134）

Author(s):

LIU Zheng; XIE Yun

（Department of Geriatrics，Chu Hsien-I Memorial Hospital，Tianjin Medical University，Tianjin Institute of Endocrinology，NHC Key Laboratory of Hormones and Development，Tianjin Key Laboratory of Metabolic Diseases，Tianjin 300134，China）

关键词:

Wnt信号通路; BMPER; 骨质疏松; MC3T3-E1细胞; 2型糖尿病

Keywords:

Wnt signaling pathway; BMPER; osteoporosis; MC3T3-E1 cell; type 2 diabetes

分类号:

R589.9

DOI:

-

文献标志码:

A

摘要:

目的：探究骨形态发生蛋白内皮细胞前体来源调节因子（BMPER）在成骨分化中的生物学作用。方法：将MC3T3-E1细胞分为对照（control）组、成骨诱导（OM）组和成骨诱导+高糖高脂（OM+HG/PA）组。采用Western印迹法检测各组细胞Runt相关转录因子2（Runx2）、Ⅰ型胶原α1（Col1α1）、BMPER的表达。将空载体对照质粒及BMPER过表达质粒转染到MC3T3-E1细胞中，将细胞分为p-NC和p-BMPER组。使用Western印迹法检测各组细胞BMPER、Runx2、Col1α1、Wnt1、Wnt3a、active β-catenin表达。碱性磷酸酶（ALP）染色检测BMPER对成骨分化的影响。应用非特异性siRNA及合成的靶向沉默BMPER小干扰RNA（siRNA）转染MC3T3-E1细胞，将细胞分为si-NC组及si-BMPER组，使用Western印迹法检测各组细胞Wnt1、Wnt3a、active β-catenin表达。结果：与OM组相比，OM+HG/PA组中Runx2、Col1α1、BMPER蛋白表达显著减少（t=7.572、 8.568、10.742，均P< 0.05）。与p-NC组相比，p-BMPER组Runx2、Col1α1、Wnt1、Wnt3a、active β-catenin蛋白表达水平显著升高（t=9.816、8.331、8.413、14.343、9.156，均P<0.05），ALP染色加深。与si-NC组相比，si-BMPER组Wnt1、Wnt3a、active β-catenin的表达显著下调（t=10.807、8.678、10.167，均P<0.05）。结论：BMPER通过Wnt/β-catenin信号通路减轻高糖高脂对MC3T3-E1细胞成骨分化的抑制。

Abstract:

Objective： To explore the biological role of bone morphogenetic protein endothelial cell precursor-derived regulator（BMPER） in osteogenic differentiation. Methods: MC3T3-E1 cells were divided into control group，osteogenic medium（OM group） and osteogenic medium+high glucose/palmitate（OM+HG/PA group）. The expression of Runt related transcription factor 2（Runx2） and type Ⅰ collagen α 1（Col1 α 1） and BMPER were detected by Western blotting. Empty vector control plasmid and BMPER overexpression plasmid were transfected into MC3T3-E1 cells，and the cells were divided into p-NC and p-BMPER groups. The expression of Runx2，Col1α1，BMPER，Wnt1，Wnt3a，active β-catenin in MC3T3-E1 cells were detected by Western blotting. The effect of BMPER on osteogenic differentiation was detected by alkaline phosphoric acid（ALP） staining.MC3T3-E1 cells were transfected with non-specific siRNA and targeted silencing BMPER siRNA. The cells were divided into si-NC group and si-BMPER group. The expression of Wnt1，Wnt3a，active β-catenin in MC3T3-E1 cells was detected by Western blotting. Results: Runx2，Col1α1 and BMPER expression was decreased in the OM+HG/PA group compared with the OM group（t=7.572，8.568，10.742，all P<0.05）. Compared with the p-NC group，Runx2，Col1α1，Wnt1，Wnt3a and active β-catenin protein levels were significantly increased in the p-BMPER group（t=9.816，8.331，8.413，14.343，9.156，all P<0.05）.BMPER overexpression deepened ALP staining. Compared with si-NC group，the expression of Wnt1，Wnt3a and active β-catenin was significantly downregulated in si-BMPER group（t=10.807，8.678，10.167，all P<0.05）.Conclusion: BMPER alleviates suppression of osteogenic differentiation by high glucose and high lipid in MC3T3-E1 cells via Wnt/β-catenin signaling pathway.

参考文献/References:

[1] SEALAND R，RAZAVI C，ADLER R A. Diabetes mellitus and osteoporosis [J]. Curr Diab Rep，2013，13（3）：411-418.
[2] KURRA S，FINK D A，SIRIS E S. Osteoporosis-associated fracture and diabetes[J]. Endocrinol Metab Clin North Am，2014，43（1）：233-243.
[3] YAMAMOTO M，SUGIMOTO T. Advanced glycation end products，diabetes，and bone strength[J]. Curr Osteoporos Rep，2016，14（6）： 320-326.
[4] ANTONOPOULOU M，BAHTIYAR G，BANERJI M A，et al. Diabetes and bone health[J]. Maturitas，2013，76（3）：253-259.
[5] MASCITELLI L，PEZZETTA F. Diabetes and osteoporotic fractures[J]. CMAJ，2007，177（11）：1391-1392.
[6] MOSER M，BINDER O，WU Y，et al. BMPER，a novel endothelial cell precursor-derived protein，antagonizes bone morphogenetic protein signaling and endothelial cell differentiation[J]. Mol Cell Biol，2003，23（16）：5664-5679.
[7] IKEYA M，KAWADA M，KIYONARI H，et al. Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis[J].Development，2006，133（22）：4463-4473.
[8] BEN-NERIAH Z，MICHAELSON-COHEN R，INBAR-FEIGENBERG M，et al. A deleterious founder mutation in the BMPER gene causes diaphanospondylodysostosis（DSD）[J]. Am J Med Genet A，2011，155A（11）：2801-2806.
[9] KUCHINSKAYA E，GRIGELIONIENE G，HAMMARSJ?魻 A，et al. Extending the phenotype of BMPER-related skeletal dysplasias to ischiospinal dysostosis[J]. Orphanet J Rare Dis，2016，11： 1.
[10] ENSRUD K E，CRANDALL C J. Osteoporosis[J]. Ann Intern Med，2017，167（3）： Itc17-Itc32.
[11] FU C，ZHANG X，YE F，et al. High insulin levels in KK-Ay diabetic mice cause increased cortical bone mass and impaired trabecular micro-structure[J].Int J Mol Sci，2015，16（4）：8213-8226.
[12] CHIODINI I，CATALANO A，GENNARI L，et al. Osteoporosis and fragility fractures in type 2 Diabetes[J]. J Diabetes Res，2020，2020： 9342696.
[13] CORTET B，LUCAS S，LEGROUX-GEROT I，et al. Bone disorders associated with diabetes mellitus and its treatments[J].Joint Bone Spine，2019，86（3）：315-320.
[14] MOHSIN S，BANIYAS M M，ALDARMAKI R S，et al. An update on therapies for the treatment of diabetes-induced osteoporosis[J]. Expert Opin Biol Ther，2019，19（9）：937-948.
[15] ZHANG Y，YANG J H. Activation of the PI3K/Akt pathway by oxidative stress mediates high glucose-induced increase of adipogenic differentiation in primary rat osteoblasts[J]. J Cell Biochem，2013，114（11）：2595-2602.
[16] FENG Z，DENG H，DU J，et al. Lentiviral-mediated RNAi targeting p38MAPK ameliorates high glucose-induced apoptosis in osteoblast MC3T3-E1 cell line[J].Indian J Exp Biol，2011，49（2）：94-104.
[17] MAO H，LI L，FAN Q，et al. Loss of bone morphogenetic protein-binding endothelial regulator causes insulin resistance[J].Nat Commun，2021，12（1）： 1927.
[18] LANE J M，RUSSELL L，KHAN S N. Osteoporosis[J]. Clin Orthop Relat Res，2000，（372）：139-150.
[19] TERAO Y，SATOMI-KOBAYASHI S，HIRATA K，et al. Involvement of Rho-associated protein kinase （ROCK） and bone morphogenetic protein-binding endothelial cell precursor-derived regulator （BMPER） in high glucose-increased alkaline phosphatase expression and activity in human coronary artery smooth muscle cells[J]. Cardiovasc Diabetol，2015，14：104.
[20] SATOMI-KOBAYASHI S，KINUGASA M，KOBAYASHI R，et al. Osteoblast-like differentiation of cultured human coronary artery smooth muscle cells by bone morphogenetic protein endothelial cell precursor-derived regulator （BMPER）[J]. J Biol Chem，2012，287（36）：30336-30345.
[21] HUANG P，YAN R，ZHANG X，et al. Activating Wnt/β-catenin signaling pathway for disease therapy：challenges and opportunities[J]. Pharmacol Ther，2019，196：79-90.
[22] JIANG T，XIA C，CHEN X，et al. Melatonin promotes the BMP9-induced osteogenic differentiation of mesenchymal stem cells by activating the AMPK/β-catenin signalling pathway[J]. Stem Cell Res Ther，2019，10（1）：408.
[23] JACKULIAK P，PAYER J. Osteoporosis，fractures，and diabetes[J]. Int J Endocrinol，2014，2014：820615.
[24] XIA K，CEN X，YU L，et al.Long noncoding RNA expression profiles during the NEL-like 1 protein-induced osteogenic differentiation[J]. J Cell Physiol，2020，235（9）：6010-6022.
[25] YU A X，XU M L，YAO P，et al.Corylin，a flavonoid derived from Psoralea Fructus，induces osteoblastic differentiation via estrogen and Wnt/β-catenin signaling pathways[J]. FASEB J，2020，34（3）：4311-4328.

相似文献/References:

备注/Memo

备注/Memo:

作者简介:刘峥(1995-)，女，硕士在读，研究方向：内分泌与代谢病；通信作者：谢云，E-mail:xieyuntj@126.com。

常用功能

更新日期/Last Update: 2022-07-20