Napabucasin Induces Mouse Bone Loss by Impairing Bone Formation via STAT3.
Napabucasin Induces Mouse Bone Loss by Impairing Bone Formation via STAT3.
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Napabucasin 通过 STAT3 损害骨形成来诱导小鼠骨丢失
DOI：
10.3389/fcell.2021.648866
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发表时间：
2021
影响因子：
5.5
通讯作者：
Jiang L
中科院分区：
文献类型：
--
作者：
Huang X;Jin A;Wang X;Gao X;Xu H;Chung M;Dai Q;Yang Y;Jiang L
新型小分子Napabucasin（也称为BBI608）被证明可以抑制由信号转导和转录激活因子3（STAT3）驱动的基因转录，这被认为是一种有前途的抗癌靶点。已经在癌症患者中进行了许多临床前研究，检查Napabucasin对癌症干细胞的选择性靶向，但很少有研究检查Napabucasin在骨骼系统中的副作用。在本研究中，我们发现在体外用Napabucasin处理骨髓间充质干细胞（BMSCs）会损害其成骨分化。在机制方面，Napabucasin通过STAT3抑制成骨基因骨钙素（Ocn）的转录而破坏BMSCs的分化。此外，通过显微CT分析，我们发现4周的Napabucasin注射诱导小鼠骨丢失。组织学分析表明，Napabucasin诱导的小鼠骨丢失是骨生成受损的结果。总之，本研究为Napabucasin对小鼠骨稳态的影响提供了证据，并揭示了其体内和体外的潜在机制。
The novel small molecule Napabucasin (also known as BBI608) was shown to inhibit gene transcription driven by Signal Transducer and Activator of Transcription 3 (STAT3), which is considered a promising anticancer target. Many preclinical studies have been conducted in cancer patients examining the selective targeting of cancer stem cells by Napabucasin, but few studies have examined side effects of Napabucasin in the skeleton system. In the present study, we found treating bone marrow mesenchymal stem cells (BMSCs) with Napabucasin in vitro impaired their osteogenic differentiation. In terms of mechanisms, Napabucasin disrupted differentiation of BMSCs by inhibiting the transcription of osteogenic gene osteocalcin (Ocn) through STAT3. Moreover, through micro-CT analysis we found 4 weeks of Napabucasin injections induced mouse bone loss. Histological analysis revealed that Napabucasin-induced bone loss in mice was the result of impaired osteogenesis. In conclusion, this study provided evidence for the effect of Napabucasin on mouse bone homeostasis and revealed its underlying mechanisms in vivo and in vitro.
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影响因子：
15.9
作者：
Bromberg, J
通讯作者：
Bromberg, J
影响因子：
4.1
作者：
Lim, R. Z. L.;Li, L.;Yong, E. L.
通讯作者：
Yong, E. L.
影响因子：
4.8
作者：
Duplomb, Laurence;Baud'huin, Marc;Heymann, Dominique
通讯作者：
Heymann, Dominique
影响因子：
4.9
作者：
Jo S;Wang SE;Lee YL;Kang S;Lee B;Han J;Sung IH;Park YS;Bae SC;Kim TH
通讯作者：
Kim TH
DOI：
10.1073/pnas.1424171112
发表时间：
2015-02-10
影响因子：
11.1
作者：
Li, Youzhi;Rogoff, Harry A.;Li, Chiang J.
通讯作者：
Li, Chiang J.