PLGA-based control release of Noggin blocks the premature fusion of cranial sutures caused by retinoic acid.

PLGA-based control release of Noggin blocks the premature fusion of cranial sutures caused by retinoic acid.
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基于 PLGA 的 Noggin 控制释放可阻止视黄酸引起的颅缝过早融合

DOI:
10.1007/s00253-018-9457-8
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发表时间:
2019-01
影响因子:
5
通讯作者:
Huang H
Huang H
中科院分区:
工程技术2区
文献类型:
--
作者:
Wang W;Zhou C;Feng Z;Li H;Zhang Y;Bao B;Cai B;Chen M;Huang H

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颅缝闭合(CS)是一种相对常见的发育障碍,即颅缝的过早和病理性融合。阐明所涉及的途径,从而治疗靶向它将有望预防CS。在本研究中,我们研究了BMP通路在全反式维甲酸(atRA)诱导的CS模型中的作用,并试图通过基于plga的控制释放在体内靶向该通路。正如预期的那样,在atRA皮下注射小鼠模型中发现后额叶缝合提前融合。进一步的机制研究表明,atRA可以抑制缝线源性间充质细胞(SMCs)的增殖,同时促进SMCs的成骨分化。此外,从BMP -2和pSMAD1/5/9的表达增加可以看出,atRA激活了BMP信号通路。重组小鼠Noggin阻断atra诱导的SMCs体外成骨作用。在体内,包被Noggin的PLGA微球明显阻止了atra诱导的缝合融合。总的来说,这些数据支持了BMP信号参与维甲酸诱导的颅缝线过早融合的假设,而基于PLGA微球的Noggin控制释放成为预防atra诱导的缝合融合的一种有希望的策略。
Craniosynostosis (CS), the premature and pathological fusion of cranial sutures, is a relatively common developmental disorder. Elucidation of the pathways involved and thus therapeutically targeting it would be promising for the prevention of CS. In the present study, we examined the role of BMP pathway in the all-trans retinoic acid (atRA)–induced CS model and tried to target the pathway in vivo via PLGA-based control release. As expected, the posterior frontal suture was found to fuse prematurely in the atRA subcutaneous injection mouse model. Further mechanism study revealed that atRA could repress the proliferation while promote the osteogenic differentiation of suture-derived mesenchymal cells (SMCs). Moreover, BMP signal pathway was found to be activated by atRA, as seen from increased expression of BMPR-2 and pSMAD1/5/9. Recombinant mouse Noggin blocked the atRA-induced enhancement of osteogenesis of SMCs in vitro. In vivo, PLGA microsphere encapsulated with Noggin significantly prevented the atRA-induced suture fusion. Collectively, these data support the hypothesis that BMP signaling is involved in retinoic acid–induced premature fusion of cranial sutures, while PLGA microsphere–based control release of Noggin emerges as a promising strategy for prevention of atRA-induced suture fusion.
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