Matricellular Protein SMOC2 Potentiates BMP9-Induced Osteogenic Differentiation in Mesenchymal Stem Cells through the Enhancement of FAK/PI3K/AKT Signaling.
Matricellular Protein SMOC2 Potentiates BMP9-Induced Osteogenic Differentiation in Mesenchymal Stem Cells through the Enhancement of FAK/PI3K/AKT Signaling.
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DOI：
10.1155/2023/5915988
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发表时间：
2023
影响因子：
4.3
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
He WG;Deng YX;Ke KX;Cao XL;Liu SY;Yang YY;Luo HH;Yao XT;Gao X;Du Y;He BC;Chen L
间充质干细胞（MSC）可以自我更新并分化为多种谱系，使MSC移植成为骨再生的一种有前途的选择。基质细胞蛋白和生长因子在调节干细胞命运中起重要作用。在这项研究中，我们研究了基质细胞蛋白SMOC 2（分泌型模块化钙结合蛋白2）对小鼠胚胎成纤维细胞（MEFs）中骨形态发生蛋白9（BMP 9）的影响，并揭示了这一过程的可能分子机制。我们发现，SMOC 2在MEFs中是可检测的，外源性SMOC 2表达增强了BMP 9诱导的成骨标志物、基质矿化和异位骨形成，而SMOC 2敲低抑制了这些作用。BMP 9增加p-FAK和p-AKT的水平，其分别通过SMOC 2和FAK沉默而增强或降低。BMP 9诱导的成骨标志物通过SMOC 2增加，并且这种增加通过沉默FAK或LY 290042部分消除。此外，我们发现一般转录因子2 I（GTF 2 I）在SMOC 2的启动子区富集，并且整合素β1在BMP 9处理的MEFs中与SMOC 2相互作用。我们的研究结果表明，SMOC 2可以通过增强FAK/PI 3 K/AKT通路来促进BMP 9诱导的成骨分化，这可能是通过促进SMOC 2和整合素β1之间的相互作用来触发的。
Mesenchymal stem cells (MSCs) can self-renew and differentiate into multiple lineages, making MSC transplantation a promising option for bone regeneration. Both matricellular proteins and growth factors play an important role in regulating stem cell fate. In this study, we investigated the effects of matricellular protein SMOC2 (secreted modular calcium-binding protein 2) on bone morphogenetic protein 9 (BMP9) in mouse embryonic fibroblasts (MEFs) and revealed a possible molecular mechanism underlying this process. We found that SMOC2 was detectable in MEFs and that exogenous SMOC2 expression potentiated BMP9-induced osteogenic markers, matrix mineralization, and ectopic bone formation, whereas SMOC2 knockdown inhibited these effects. BMP9 increased the levels of p-FAK and p-AKT, which were either enhanced or reduced by SMOC2 and FAK silencing, respectively. BMP9-induced osteogenic markers were increased by SMOC2, and this increase was partially abolished by silencing FAK or LY290042. Furthermore, we found that general transcription factor 2I (GTF2I) was enriched at the promoter region of SMOC2 and that integrin β1 interacted with SMOC2 in BMP9-treated MEFs. Our findings demonstrate that SMOC2 can promote BMP9-induced osteogenic differentiation by enhancing the FAK/PI3K/AKT pathway, which may be triggered by facilitating the interaction between SMOC2 and integrin β1.
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影响因子：
14.8
作者：
Luo, Jinyong;Deng, Zhong-Liang;He, Tong-Chuan
通讯作者：
He, Tong-Chuan
SMOC2 变体通过竞争性结合 BMPR1B 抑制 BMP 信号传导并导致生长板缺陷
影响因子：
4.1
作者：
Long, Feng;Shi, Hongbiao;Liu, Qiji
通讯作者：
Liu, Qiji
β-肌动蛋白的丧失会导致成骨重编程过程中成骨细胞分化基因的加速矿化和失调。
DOI：
10.1002/advs.202002261
发表时间：
2020-12
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子：
--
作者：
Gjorgjieva T;Xie X;Commins P;Pasricha R;Mahmood SR;Gunsalus KC;Naumov P;Percipalle P
通讯作者：
Percipalle P
DOI：
10.1016/j.cub.2017.04.057
发表时间：
2017-06-05
期刊：
Current biology : CB
影响因子：
--
作者：
Marchant TW;Johnson EJ;McTeir L;Johnson CI;Gow A;Liuti T;Kuehn D;Svenson K;Bermingham ML;Drögemüller M;Nussbaumer M;Davey MG;Argyle DJ;Powell RM;Guilherme S;Lang J;Ter Haar G;Leeb T;Schwarz T;Mellanby RJ;Clements DN;Schoenebeck JJ
通讯作者：
Schoenebeck JJ
影响因子：
4.8
作者：
Barker, TH;Baneyx, G;Sage, EH
通讯作者：
Sage, EH