• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

AP2a 通过抑制 YAP/RUNX2 复合物和 BARX1 转录来增强间充质干细胞的成骨分化。

AP2a enhanced the osteogenic differentiation of mesenchymal stem cells by inhibiting the formation of YAP/RUNX2 complex and BARX1 transcription.

机构信息

Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory for Tooth Regeneration and Function Reconstruction of Oral Tissues, Capital Medical University School of Stomatology, Beijing, China.

Department of Implant Dentistry, Capital Medical University School of Stomatology, Beijing, China.

出版信息

Cell Prolif. 2019 Jan;52(1):e12522. doi: 10.1111/cpr.12522. Epub 2018 Nov 15.

DOI:10.1111/cpr.12522
PMID:30443989
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6430486/
Abstract

OBJECTIVES

Bone regeneration by bone tissue engineering is a therapeutic option for bone defects. Improving the osteogenic differentiation of mesenchymal stem cells (MSCs) is essential for successful bone regeneration. We previously showed that AP2a enhances the osteogenic differentiation in MSCs. The present study investigated the mechanism of how AP2a regulates the direct differentiation.

MATERIALS AND METHODS

Co-immunoprecipitation and ChIP assays were carried out to investigate the underlying mechanism in MSCs differentiation. The osteogenic differentiation potential was determined by mineralization ability and the expression of osteogenic marker in vitro and the in vivo bone-like tissue generation in nude mice.

RESULTS

We show that AP2a can compete with RUNX2, a key transcription factor in osteogenic differentiation, to recruit YAP and release the inhibition of RUNX2 activity from YAP by forming YAP-AP2a protein complex. YAP-AP2a protein complex also interacts with the BARX1 promoter through AP2a, inhibit the transcription of BARX1. Moreover, BARX1 inhibits osteogenic differentiation of MSCs.

CONCLUSIONS

Our discoveries revealed that AP2a may regulate the osteogenic differentiation in an indirect way through competing with RUNX2 to relieve the RUNX2 activity which inhibited by YAP, and also in a direct way via targeting the BARX1 and directly repressed its transcription. Thus, our discoveries shed new light on the mechanism of direct differentiation of MSCs and provide candidate targets for improving the osteogenic differentiation and enhancing bone tissue regeneration.

摘要

目的

通过骨组织工程进行骨再生是治疗骨缺损的一种选择。提高间充质干细胞（MSCs）的成骨分化能力对于成功的骨再生至关重要。我们之前表明 AP2a 可增强 MSCs 的成骨分化。本研究探讨了 AP2a 调节直接分化的机制。

材料和方法

通过共免疫沉淀和 ChIP 测定来研究 MSC 分化中的潜在机制。通过体外矿化能力和骨形成标志物的表达以及裸鼠体内骨样组织的生成来确定成骨分化潜能。

结果

我们表明，AP2a 可以与 RUNX2（成骨分化的关键转录因子）竞争，通过形成 YAP-AP2a 蛋白复合物，招募 YAP 并释放 YAP 对 RUNX2 活性的抑制。YAP-AP2a 蛋白复合物还通过 AP2a 与 BARX1 启动子相互作用，抑制 BARX1 的转录。此外，BARX1 抑制 MSCs 的成骨分化。

结论

我们的发现表明，AP2a 可能通过与 RUNX2 竞争来间接调节成骨分化，从而缓解被 YAP 抑制的 RUNX2 活性，并且还可以通过靶向 BARX1 并直接抑制其转录来直接调节成骨分化。因此，我们的发现为 MSCs 的直接分化机制提供了新的见解，并为提高成骨分化和增强骨组织再生提供了候选靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52e0/6430486/ca7b73a10776/CPR-52-e12522-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52e0/6430486/909c634d4a89/CPR-52-e12522-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52e0/6430486/41cafdc86c3d/CPR-52-e12522-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52e0/6430486/c98693b4dd9b/CPR-52-e12522-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52e0/6430486/e388c5635f1b/CPR-52-e12522-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52e0/6430486/ca7b73a10776/CPR-52-e12522-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52e0/6430486/909c634d4a89/CPR-52-e12522-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52e0/6430486/41cafdc86c3d/CPR-52-e12522-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52e0/6430486/c98693b4dd9b/CPR-52-e12522-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52e0/6430486/e388c5635f1b/CPR-52-e12522-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52e0/6430486/ca7b73a10776/CPR-52-e12522-g005.jpg

相似文献

1
AP2a enhanced the osteogenic differentiation of mesenchymal stem cells by inhibiting the formation of YAP/RUNX2 complex and BARX1 transcription.AP2a 通过抑制 YAP/RUNX2 复合物和 BARX1 转录来增强间充质干细胞的成骨分化。
Cell Prolif. 2019 Jan;52(1):e12522. doi: 10.1111/cpr.12522. Epub 2018 Nov 15.
2
Homeobox C10 inhibits the osteogenic differentiation potential of mesenchymal stem cells.同源盒C10抑制间充质干细胞的成骨分化潜能。
Connect Tissue Res. 2018 May;59(3):201-211. doi: 10.1080/03008207.2017.1341496. Epub 2017 Aug 1.
3
Enhanced bone tissue regeneration of a biomimetic cellular scaffold with co-cultured MSCs-derived osteogenic and angiogenic cells.仿生细胞支架共培养 MSC 源性成骨和成血管细胞增强骨组织再生。
Cell Prolif. 2019 Sep;52(5):e12658. doi: 10.1111/cpr.12658. Epub 2019 Jul 11.
4
Pax2 is essential for proliferation and osteogenic differentiation of mouse mesenchymal stem cells via Runx2.Pax2 通过 Runx2 对小鼠间充质干细胞的增殖和成骨分化是必需的。
Exp Cell Res. 2018 Oct 15;371(2):342-352. doi: 10.1016/j.yexcr.2018.08.026. Epub 2018 Aug 23.
5
FHL2 mediates dexamethasone-induced mesenchymal cell differentiation into osteoblasts by activating Wnt/beta-catenin signaling-dependent Runx2 expression.FHL2通过激活Wnt/β-连环蛋白信号通路依赖的Runx2表达，介导地塞米松诱导间充质细胞分化为成骨细胞。
FASEB J. 2008 Nov;22(11):3813-22. doi: 10.1096/fj.08-106302. Epub 2008 Jul 24.
6
Iron overload inhibits osteogenic commitment and differentiation of mesenchymal stem cells via the induction of ferritin.铁过载通过诱导铁蛋白抑制间充质干细胞的成骨定向分化。
Biochim Biophys Acta. 2016 Sep;1862(9):1640-9. doi: 10.1016/j.bbadis.2016.06.003. Epub 2016 Jun 7.
7
BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network.骨形态发生蛋白2向成骨谱系的定向分化涉及由远端缺失同源盒3（DLX3）和一个同源结构域转录网络激活的Runx2。
J Biol Chem. 2006 Dec 29;281(52):40515-26. doi: 10.1074/jbc.M604508200. Epub 2006 Oct 23.
8
Impact of zinc fingers and homeoboxes 3 on the regulation of mesenchymal stem cell osteogenic differentiation.锌指和同源盒蛋白 3 对间充质干细胞成骨分化调控的影响。
Stem Cells Dev. 2011 Sep;20(9):1539-47. doi: 10.1089/scd.2010.0279. Epub 2011 Feb 24.
9
Myocilin stimulates osteogenic differentiation of mesenchymal stem cells through mitogen-activated protein kinase signaling.肌间线蛋白通过丝裂原活化蛋白激酶信号通路刺激间充质干细胞的成骨分化。
J Biol Chem. 2013 Jun 7;288(23):16882-16894. doi: 10.1074/jbc.M112.422972. Epub 2013 Apr 29.
10
Knockdown of SLC41A1 magnesium transporter promotes mineralization and attenuates magnesium inhibition during osteogenesis of mesenchymal stromal cells.敲低溶质载体家族41成员1（SLC41A1）镁转运体可促进间充质基质细胞成骨过程中的矿化并减弱镁的抑制作用。
Stem Cell Res Ther. 2017 Feb 21;8(1):39. doi: 10.1186/s13287-017-0497-2.

引用本文的文献

1
A metamaterial scaffold beyond modulus limits: enhanced osteogenesis and angiogenesis of critical bone defects.一种超越模量限制的超材料支架：促进关键骨缺损的成骨和血管生成
Nat Commun. 2025 Mar 4;16(1):2180. doi: 10.1038/s41467-025-57609-9.
2
Hippo Signaling Pathway Involvement in Osteopotential Regulation of Murine Bone Marrow Cells Under Simulated Microgravity.Hippo 信号通路在模拟微重力条件下对小鼠骨髓细胞成骨潜能调控中的作用。
Cells. 2024 Nov 19;13(22):1921. doi: 10.3390/cells13221921.
3
TAZ reverses the inhibitory effects of LPS on the osteogenic differentiation of human periodontal ligament stem cells through the NF-κB signaling pathway.

本文引用的文献

1
Nonunion fractures, mesenchymal stem cells and bone tissue engineering.骨折不愈合、间充质干细胞和骨组织工程。
J Biomed Mater Res A. 2018 Sep;106(9):2552-2562. doi: 10.1002/jbm.a.36433. Epub 2018 May 2.
2
Surgical Outcomes After Limb-Sparing Resection and Reconstruction for Pelvic Sarcoma: A Systematic Review.骨盆肉瘤保肢切除与重建术后的手术结果：一项系统评价
JBJS Rev. 2018 Apr;6(4):e10. doi: 10.2106/JBJS.RVW.17.00072.
3
Reconstruction of condyles by transport distraction osteogenesis: 3 case report with complication management.
TAZ 通过 NF-κB 信号通路逆转 LPS 对人牙周膜干细胞成骨分化的抑制作用。
BMC Oral Health. 2024 Jun 26;24(1):733. doi: 10.1186/s12903-024-04497-y.
4
In Vitro Modelling of Osteogenesis Imperfecta with Patient-Derived Induced Mesenchymal Stem Cells.利用患者来源的诱导间充质干细胞体外构建成骨不全症模型。
Int J Mol Sci. 2024 Mar 18;25(6):3417. doi: 10.3390/ijms25063417.
5
YAP/TAZ as Molecular Targets in Skeletal Muscle Atrophy and Osteoporosis.YAP/TAZ作为骨骼肌萎缩和骨质疏松症的分子靶点
Aging Dis. 2024 Mar 14;16(1):299-320. doi: 10.14336/AD.2024.0306.
6
Hippo-YAP/TAZ signaling in osteogenesis and macrophage polarization: Therapeutic implications in bone defect repair.Hippo-YAP/TAZ信号通路在骨生成和巨噬细胞极化中的作用：对骨缺损修复的治疗意义
Genes Dis. 2023 Jan 16;10(6):2528-2539. doi: 10.1016/j.gendis.2022.12.012. eCollection 2023 Nov.
7
Mechanobiology-informed biomaterial and tissue engineering strategies for influencing skeletal stem and progenitor cell fate.基于力学生物学的生物材料及组织工程策略对骨骼干/祖细胞命运的影响
Front Physiol. 2023 Jul 13;14:1220555. doi: 10.3389/fphys.2023.1220555. eCollection 2023.
8
METTL3 Promotes Osteo/Odontogenic Differentiation of Stem Cells by Inhibiting miR-196b-5p Maturation.METTL3通过抑制miR-196b-5p成熟促进干细胞的成骨/牙源性分化。
Stem Cells Int. 2023 Jun 7;2023:8992284. doi: 10.1155/2023/8992284. eCollection 2023.
9
The effect of ROS-YAP crosstalk on osteoimmune response orchestrating osteogenesis.ROS-YAP 串扰对调控成骨的骨免疫反应的影响。
Cell Cycle. 2023 Jun;22(11):1391-1405. doi: 10.1080/15384101.2023.2211830. Epub 2023 May 9.
10
Cell-based therapies for rheumatoid arthritis: opportunities and challenges.类风湿关节炎的细胞疗法：机遇与挑战。
Ther Adv Musculoskelet Dis. 2022 May 23;14:1759720X221100294. doi: 10.1177/1759720X221100294. eCollection 2022.
经骨搬运牵张成骨重建髁突：3 例病例报告及并发症处理。
J Stomatol Oral Maxillofac Surg. 2018 Sep;119(4):348-353. doi: 10.1016/j.jormas.2018.04.007. Epub 2018 Apr 21.
4
Skeletal cell YAP and TAZ combinatorially promote bone development.YAP 和 TAZ 共同促进骨骼细胞的骨发育。
FASEB J. 2018 May;32(5):2706-2721. doi: 10.1096/fj.201700872R. Epub 2018 Jan 10.
5
Effect of titanium ions on the Hippo/YAP signaling pathway in regulating biological behaviors of MC3T3-E1 osteoblasts.钛离子对 Hippo/YAP 信号通路调控 MC3T3-E1 成骨细胞生物学行为的影响。
J Appl Toxicol. 2018 Jun;38(6):824-833. doi: 10.1002/jat.3590. Epub 2018 Jan 29.
6
AP-2α and AP-2β cooperatively orchestrate homeobox gene expression during branchial arch patterning.在鳃弓模式形成过程中，AP-2α和AP-2β共同协调同源框基因的表达。
Development. 2018 Jan 25;145(2):dev157438. doi: 10.1242/dev.157438.
7
Acoustic tweezing cytometry enhances osteogenesis of human mesenchymal stem cells through cytoskeletal contractility and YAP activation.声学镊子细胞术通过细胞骨架收缩性和YAP激活增强人间充质干细胞的成骨作用。
Biomaterials. 2017 Jul;134:22-30. doi: 10.1016/j.biomaterials.2017.04.039. Epub 2017 Apr 22.
8
YAP-mediated mechanotransduction regulates osteogenic and adipogenic differentiation of BMSCs on hierarchical structure.YAP介导的机械转导调节骨髓间充质干细胞在分级结构上的成骨和成脂分化。
Colloids Surf B Biointerfaces. 2017 Apr 1;152:344-353. doi: 10.1016/j.colsurfb.2017.01.039. Epub 2017 Jan 23.
9
TFII-I and AP2α Co-Occupy the Promoters of Key Regulatory Genes Associated with Craniofacial Development.TFII-I与AP2α共同占据与颅面发育相关的关键调控基因的启动子区域。
Cleft Palate Craniofac J. 2018 Jul;55(6):865-870. doi: 10.1597/15-214. Epub 2018 Feb 26.
10
Gold nanoparticle size and shape influence on osteogenesis of mesenchymal stem cells.金纳米颗粒的尺寸和形状对间充质干细胞成骨作用的影响。
Nanoscale. 2016 Apr 21;8(15):7992-8007. doi: 10.1039/c5nr08808a.