TAZ promotes osteogenic differentiation of mesenchymal stem cells line C3H10T1/2, murine multi-lineage cells lines C2C12, and MEFs induced by BMP9.
TAZ promotes osteogenic differentiation of mesenchymal stem cells line C3H10T1/2, murine multi-lineage cells lines C2C12, and MEFs induced by BMP9.
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TAZ 促进间充质干细胞系 C3H10T1/2、小鼠多谱系细胞系 C2C12 和 BMP9 诱导的 MEF 的成骨分化
DOI：
10.1038/s41420-022-01292-y
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发表时间：
2022-12-27
影响因子：
7
通讯作者：
Luo, Jinyong
中科院分区：
文献类型：
--
作者：
Huang, Huakun;Lu, Qiuping;Ye, Caihong;Wei, Mengqi;Yang, Chunmei;Zhang, Lulu;Huang, Yanran;Luo, Xiaoji;Luo, Jinyong
骨形态发生蛋白9（BMP 9）又称生长分化因子2（GDF-2），是BMP家族中促进成骨分化作用最强的细胞因子，具有广泛的临床应用价值。然而，BMP 9促进成骨分化的机制尚不清楚。TAZ是一种转录辅激活因子，对细胞增殖、分化和干细胞自我更新具有重要作用。本研究观察了TAZ对BMP 9诱导间充质干细胞系C3 H10 T12（MSCs）、小鼠多系细胞系C2 C12和MEFs（MMCs）成骨分化的影响，并探讨其可能的作用机制。本研究发现BMP 9诱导TAZ的表达并促进其核转位。同时，我们的研究发现，Ad-TAZ和TAZ激动剂TM-25659可以增强BMP 9诱导的MSCs和MMCs的成骨分化。相反，Ad-si-TAZ和TAZ的抑制剂verteporfin具有相反的作用。同样地，通过在裸鼠皮下移植MSC证实了TAZ对BMP 9诱导的体内异位骨形成的促进作用。此外，我们已经检测到TAZ可能增加由BMP 9诱导的Smad 1/5/8、p38、ERK 1/2和JNK的磷酸化水平。此外，我们还发现TAZ增加了BMP 9诱导的β-catenin的总蛋白水平。综上所述，我们的研究结果有力地表明，TAZ将通过多个信号通路促进BMP 9诱导的MSC和MMCs的成骨分化。
Bone morphogenetic protein 9 (BMP9), also named as growth differentiation factor 2 (GDF-2), is the strongest cytokine that promotes osteogenic differentiation in the BMP family, and has broad clinical application value. Nevertheless, the mechanism of BMP9 promotes osteogenic differentiation remain unclear. TAZ, a transcriptional co-activator, has great effects on cell proliferation, differentiation, and stem cell self-renewal. In this research, we investigated the effects of TAZ in BMP9-induced osteogenic differentiation of mesenchymal stem cell line C3H10T1/2 (MSCs) and murine multi-lineage cell lines C2C12 and MEFs (MMCs) and explored its possible mechanisms. This study has found that BMP9 induces the expression of TAZ and promotes its nuclear translocation. Meanwhile, our study found that Ad-TAZ and TM-25659, a TAZ agonist, can enhance the osteogenic differentiation of MSCs and MMCs induced by BMP9. Conversely, Ad-si-TAZ and verteporfin, an inhibitor of TAZ, have the contradictory effect. Likewise, the promotion of TAZ to the BMP9-induced ectopic bone formation in vivo was confirmed by the subcutaneous transplantation of MSCs in nude mice. Furthermore, we have detected that TAZ might increase the levels of the phosphorylation of Smad1/5/8, p38, ERK1/2, and JNK induced by BMP9. Additionally, we also found that TAZ increased the total protein level of β-catenin induced by BMP9. In summary, our results strongly indicated that TAZ will promote the osteogenic differentiation in MSCs and MMCs induced by BMP9 through multiple signal pathways.
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影响因子：
7.5
作者：
Huang Y;He B;Wang L;Yuan B;Shu H;Zhang F;Sun L
通讯作者：
Sun L
影响因子：
2.7
作者：
Katayama, Yoshito;Matsuyama, Yukihiro;Ishiguro, Naoki
通讯作者：
Ishiguro, Naoki
影响因子：
4.1
作者：
Byun, Mi Ran;Jeong, Hana;Hong, Jeong-Ho
通讯作者：
Hong, Jeong-Ho
DOI：
10.1038/s41374-018-0087-7
发表时间：
2019-01
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Cui J;Zhang W;Huang E;Wang J;Liao J;Li R;Yu X;Zhao C;Zeng Z;Shu Y;Zhang R;Yan S;Lei J;Yang C;Wu K;Wu Y;Huang S;Ji X;Li A;Gong C;Yuan C;Zhang L;Liu W;Huang B;Feng Y;An L;Zhang B;Dai Z;Shen Y;Luo W;Wang X;Huang A;Luu HH;Reid RR;Wolf JM;Thinakaran G;Lee MJ;He TC
通讯作者：
He TC
影响因子：
5.1
作者：
Kang, Q;Sun, MH;He, TC
通讯作者：
He, TC