[1]解静,汪永新.MSX1基因调控Wnt/β-catenin通路刺激成骨分化和骨形成机制实验研究[J].陕西医学杂志,2025,54(6):754-758.[doi:DOI:10.3969/j.issn.1000-7377.2025.06.006]
 XIE Jing,WANG Yongxin.Mechanism of MSX1 regulating Wnt/β-catenin pathway to stimulate osteogenic differentiation and bone formation[J].,2025,54(6):754-758.[doi:DOI:10.3969/j.issn.1000-7377.2025.06.006]
点击复制

MSX1基因调控Wnt/β-catenin通路刺激成骨分化和骨形成机制实验研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年6期
页码:
754-758
栏目:
基础研究
出版日期:
2025-06-05

文章信息/Info

Title:
Mechanism of MSX1 regulating Wnt/β-catenin pathway to stimulate osteogenic differentiation and bone formation
作者:
解静汪永新
(新疆医科大学第一附属医院,新疆 乌鲁木齐 830054)
Author(s):
XIE JingWANG Yongxin
(The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)
关键词:
骨质疏松症同源盒基因1MC3T3-E1细胞成骨分化骨形成Wnt/β-catenin通路
Keywords:
OsteoporosisMSX1MC3T3-E1 cellsOsteogenic differentiationBone formationWnt/β-catenin pathway
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2025.06.006
文献标志码:
A
摘要:
目的:探究同源盒基因1(MSX1)调控Wnt/β-catenin通路刺激成骨分化和骨形成的机制。方法:对MC3T3-E1细胞使用成骨诱导培养基(OIM)进行成骨培养,诱导分化后分为对照组、小干扰RNA-阴性对照组(sh-NC组)及sh-MSX1组。实时荧光定量PCR(RT-qPCR)检测MSX1及成骨相关基因[胶原蛋白Ⅰ型(Col1A1)、骨桥蛋白(OPN)、碱性磷酸酶(ALP)、骨钙蛋白(OCN)];流式细胞仪检测细胞凋亡率;茜素红S染色鉴定MC3T3-E1细胞钙化结节;检测ALP活性;Western blot检测Wnt/β-catenin信号通路相关蛋白。进一步对MC3T3-E1细胞使用Wnt/β-catenin通路激动剂SKL2001后进行分组,分别为对照组、激动剂组、sh-MSX1组和sh-MSX1组+激动剂组,RT-qPCR检测成骨相关基因。结果:与诱导分化第0天比较,OIM以时间依赖性的方式升高了MC3T3-E1细胞中MSX1 mRNA的表达。sh-MSX1组细胞凋亡率高于sh-NC组,ALP活性及钙化面积低于sh-NC组(均P<0.05)。sh-MSX1组Col1A1、OPN、ALP及OCN mRNA表达低于sh-NC组,Wnt1、Wnt3a、β-catenin蛋白表达低于sh-NC组(均P<0.05)。与对照组比较,激动剂组成骨相关基因表达升高,sh-MSX1组降低(均P<0.05)。sh-MSX1组+激动剂组成骨相关基因表达高于sh-MSX1组(均P<0.05)。结论:敲低MSX1可促进MC3T3-E1细胞凋亡,并通过抑制Wnt/β-catenin通路激活降低MC3T3-E1细胞成骨分化和骨形成能力。
Abstract:
Objective:To investigate the mechanism of msh homeobox gene 1 (MSX1) regulating Wnt/β-catenin pathway to stimulate osteogenic differentiation and bone formation.Methods:MC3T3-E1 cells were cultured using osteogenic induction medium (OIM) and divided into three groups:control group,small interference RNA-negative control group (sh-NC group) and sh-MSX1 group.MSX1 and osteogenic genes (Col1A1,OPN,ALP,OCN) were detected by RT-qPCR.The apoptosis rate was detected by flow cytometry.Alizarin red S staining was used to detect calcified nodules in MC3T3-E1 cells,and ALP activity was detected.Western blot was used to detect Wnt/β-catenin signaling pathway-related proteins.MC3T3-E1 cells were further divided into control group,agonist group,sh-MSX1 group and sh-MSX1+agonist group after receiving Wnt/β-catenin pathway agonist SKL2001,and bone formation related genes were detected by RT-qPCR.Results:Compared with day 0,OIM increased MSX1 mRNA expression in MC3T3-E1 cells in a time-dependent manner.The apoptosis rate of sh-MSX1 group was significantly higher than that of sh-NC group,and ALP activity and calcified area of sh-MSX1 group were lower than those of sh-NC group (all P<0.05).The mRNA expressions of Col1A1,OPN,ALP and OCN in sh-MSX1 group were less than those in the sh-NC group,and the protein expressions of Wnt1,Wnt3a and β-catenin in sh-MSX1 group were lower than those in sh-NC group (all P<0.05).Compared with the control group,the expression of bone-related genes was increased in the agonist group and decreased in the sh-MSX1 group (all P<0.05).The expression of bone-related genes in the sh-MSX1+agonist group was higher than that in the sh-MSX1 group (all P<0.05).Conclusion:Knockdown of MSX1 can promote the apoptosis of MC3T3-E1 cells,and reduce the osteogenic differentiation and bone formation ability of MC3T3-E1 cells by inhibiting the activation of Wnt/β-catenin pathway.

参考文献/References:

[1]GAO S,ZHAO Y.Quality of life in postmenopausal women with osteoporosis:A systematic review and meta-analysis[J].Qual Life Res,2023,32(6):1551-1565.
[2]吕浩,张舸,胡芷苜,等.炎症、代谢物与骨质疏松症[J].中国组织工程研究,2025,29(17):3697-3704.
[3]BIXEL M G,SIVARAJ K K,TIMMEN M,et al.Angiogenesis is uncoupled from osteogenesis during calvarial bone regeneration[J].Nat Commun,2024,15(1):4575.
[4]MAHAJAN A,BHATTACHARYYA S.Immunomodulation by mesenchymal stem cells during osteogenic differentiation:Clinical implications during bone regeneration[J].Mol Immunol,2023,164:143-152.
[5]张伟杰,刘向晖,杨玉娥.同源盒基因调控先天缺牙的研究进展[J].国际口腔医学杂志,2024,51(3):374-380.
[6]ZHANG B,WANG Z,GAO K,et al.MSX1 regulates goat endometrial function by altering the plasma membrane transformation of endometrial epithelium cells during early pregnancy[J].Int J Mol Sci,2023,24(4):4121.
[7]LEE J M,QIN C,CHAI O H,et al.MSX1 drives tooth morphogenesis through controlling Wnt signaling activity[J].J Dent Res,2022,101(7):832-839.
[8]LIU J,XIAO Q,XIAO J,et al.Wnt/beta-catenin signalling:Function,biological mechanisms,and therapeutic opportunities[J].Signal Transduct Target Ther,2022,7(1):3.
[9]OH W T,YANG Y S,XIE J,et al.Wnt-modulating gene silencers as a gene therapy for osteoporosis,bone fracture,and critical-sized bone defects[J].Mol Ther,2023,31(2):435-453.
[10]AIBAR-ALMAZAN A,VOLTES-MARTINEZ A,CASTELLOTE-CABALLERO Y,et al.Current status of the diagnosis and management of osteoporosis[J].Int J Mol Sci,2022,23(16):9465.
[11]李淼,李蕊,程新春.骨质疏松症合并常见老年综合征的研究进展[J].基础医学与临床,2025,45(1):112-115.
[12]昌震,李大同,杨小彬,等.奇壬醇对骨质疏松症的治疗作用及机制研究进展[J].陕西医学杂志,2022,51(9):1167-1170.
[13]LIU J,CHANG X,DONG D.MicroRNA-181a-5p curbs osteogenic differentiation and bone formation partially through impairing runx1-dependent inhibition of AIF-1 transcription[J].Endocrinol Metab (Seoul),2023,38(1):156-173.
[14]张婷,刘丹,贠丹丹,等.基于Wnt/β-连环蛋白通路探究金天格对肿瘤坏死因子-α诱导的小鼠MC3T3E1细胞生物学功能的影响实验研究[J].陕西医学杂志,2024,53(6):744-777,753.
[15]周勇,朱明会,黄旭瑶,等.探讨MSX1基因缺失导致的牙发育异常的机制及可能的信号通路[J].临床口腔医学杂志,2021,37(12):716-719.
[16]ZHANG X,JIANG W,XIE C,et al.Msx1+ stem cells recruited by bioactive tissue engineering graft for bone regeneration[J].Nat Commun,2022,13(1):5211.
[17]SHEMSHADI S,SHEKARI F,ESLAMINEJAD M B,et al.Extracellular vesicles derived from Msh homeobox 1 (Msx1)-overexpressing mesenchymal stem cells improve digit tip regeneration in an amputee mice model[J].Sci Rep,2024,14(1):23538.
[18]YU L,SUI B,FAN W,et al.Exosomes derived from osteogenic tumor activate osteoclast differentiation and concurrently inhibit osteogenesis by transferring COL1A1-targeting miRNA-92a-1-5p[J].J Extracell Vesicles,2021,10(3):e12056.
[19]RUAN H,ZHANG H,FENG J,et al.Inhibition of Caspase-1-mediated pyroptosis promotes osteogenic differentiation,offering a therapeutic target for osteoporosis[J].Int Immunopharmacol,2023,124(Pt B):110901.
[20]HWANG J H,PARK Y S,KIM H S,et al.Yam-derived exosome-like nanovesicles stimulate osteoblast formation and prevent osteoporosis in mice[J].J Control Release,2023,355:184-198.
[21]GOTO N,FUJIMOTO K,FUJII S,et al.Role of MSX1 in osteogenic differentiation of human dental pulp stem cells[J].Stem Cells Int,2016,2016:8035759.
[22]吴雪,张惜燕,李翠娟,等.固本活血壮骨颗粒通过Wnt/LRP5/β-catenin信号通路改善糖皮质激素性骨质疏松症机制研究[J].陕西中医,2023,44(12):1693-1697.
[23]SHEN G,REN H,SHANG Q,et al.Foxf1 knockdown promotes BMSC osteogenesis in part by activating the Wnt/beta-catenin signalling pathway and prevents ovariectomy-induced bone loss[J].EBioMedicine,2020,52:102626.
[24]AHMAD M,HAFFNER-LUNTZER M,SCHOPPA A,et al.Mechanical induction of osteoanabolic Wnt1 promotes osteoblast differentiation via plat[J].FASEB J,2024,38(4):e23489.
[25]武建萍,蔡学梅,张亚菊,等.电针康复干预Wnt/β-catenin通路对骨质疏松大鼠的影响[J].中国骨质疏松杂志,2024,30(11):1568-1573.

相似文献/References:

[1]李 洺,赵 宇△,马 丁,等.女性绝经后骨质疏松症患者血清铁蛋白、同源拮抗物表达水平及临床意义*[J].陕西医学杂志,2020,49(10):1266.[doi:DOI:10.3969/j.issn.1000-7377.2020.10.017]
 LI Ming,ZHAO Yu,MA Ding,et al.Expression and clinical significance of serum ferritin and B-cell lymphoma factor 2 homologous antagonist in postmenopausal women with osteoporosis[J].,2020,49(6):1266.[doi:DOI:10.3969/j.issn.1000-7377.2020.10.017]
[2]昌 震,李大同,杨小彬,等.奇壬醇对骨质疏松症的治疗作用及机制研究进展[J].陕西医学杂志,2022,51(9):1167.[doi:DOI:10.3969/j.issn.1000-7377.2022.09.029]
 CHANG Zhen,LI Datong,YANG Xiaobin,et al.Research progress on therapeutic effect and mechanism of Kirenol on osteoporosis[J].,2022,51(6):1167.[doi:DOI:10.3969/j.issn.1000-7377.2022.09.029]
[3]张亮亮,赵程锦,周煜虎,等.积雪草酸对大鼠绝经后骨质疏松症的治疗作用及机制研究[J].陕西医学杂志,2023,52(12):1624.[doi:DOI:10.3969/j.issn.1000-7377.2023.12.002]
 ZHANG Liangliang,ZHAO Chengjin,ZHOU Yuhu,et al.Therapeutic effect and mechanism of asiatic acid on postmenopausal osteoporosis in rats[J].,2023,52(6):1624.[doi:DOI:10.3969/j.issn.1000-7377.2023.12.002]
[4]彭 赛,卢丛兰,孙中洋.人工智能在骨质疏松症诊疗中的应用进展[J].陕西医学杂志,2024,(3):425.[doi:DOI:10.3969/j.issn.1000-7377.2024.03.030]
 PENG Sai,LU Conglan,SUN Zhongyang.Advances in application of artificial intelligence in diagnosis and treatment of osteoporosis[J].,2024,(6):425.[doi:DOI:10.3969/j.issn.1000-7377.2024.03.030]
[5]周浩然,郑志杰,李瑞忠.血清PTX3、ANXA2、IL-33在老年骨质疏松症患者中的表达变化及其预测并发骨折价值[J].陕西医学杂志,2025,54(6):819.[doi:DOI:10.3969/j.issn.1000-7377.2025.06.019]
 ZHOU Haoran,ZHENG Zhijie,LI Ruizhong.Expression of serum PTX3,ANXA2 and IL-33 in elderly patients with osteoporosis and their predictive value for fracture[J].,2025,54(6):819.[doi:DOI:10.3969/j.issn.1000-7377.2025.06.019]

备注/Memo

备注/Memo:
国家自然科学基金资助项目(81401806)
更新日期/Last Update: 2025-06-04