Suppression of osteoclast multinucleation via a posttranscriptional regulation-based spatiotemporally selective delivery system.
Suppression of osteoclast multinucleation via a posttranscriptional regulation-based spatiotemporally selective delivery system.
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通过基于转录后调控的时空选择性递送系统抑制破骨细胞多核。
DOI：
10.1126/sciadv.abn3333
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发表时间：
2022-07
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
单核前破骨细胞（pOC）过度融合导致多核成熟破骨细胞的冗余，导致骨质疏松等溶骨性疾病。不幸的是，目前临床上可用的药物完全抑制破骨细胞，从而干扰正常的生理性骨转换。 pOC 特异性调节可能更适合维持骨稳态。在这里，circBBS9（一种先前未鉴定的环状RNA）被发现通过pOC中的circBBS9/miR-423-3p/Traf6轴发挥调节作用。为了克服时空 RNA 递送至细胞的长期挑战，我们构建了仿生纳米粒子，以实现 circBBS9 的 pOC 特异性靶向递送。提取 pOC 膜 (POCM) 以伪装阳离子聚合物，以干扰 circBBS9 (POCM-NPs@siRNA/shRNAcircBBS9) 的 RNA。 POCM-NP 赋予纳米载体更高的稳定性、精确的 pOC 靶向、融合吸收和活性氧响应释放。总之，我们的研究结果可能为多核细胞相关疾病提供一种替代策略，其中涉及通过时空选择性递送系统限制单核细胞多核化。时空选择性递送系统通过转录后调节限制破骨细胞多核。
Redundancy of multinucleated mature osteoclasts, which results from the excessive fusion of mononucleated preosteoclasts (pOCs), leads to osteolytic diseases such as osteoporosis. Unfortunately, the currently available clinical drugs completely inhibit osteoclasts, thus interfering with normal physiological bone turnover. pOC-specific regulation may be more suitable for maintaining bone homeostasis. Here, circBBS9, a previously unidentified circular RNA, was found to exert regulatory effects via the circBBS9/miR-423-3p/Traf6 axis in pOCs. To overcome the long-standing challenge of spatiotemporal RNA delivery to cells, we constructed biomimetic nanoparticles to achieve the pOC-specific targeted delivery of circBBS9. pOC membranes (POCMs) were extracted to camouflage cationic polymer for RNA interference with circBBS9 (POCM-NPs@siRNA/shRNAcircBBS9). POCM-NPs endowed the nanocarriers with improved stability, accurate pOC targeting, fusogenic uptake, and reactive oxygen species–responsive release. In summary, our findings may provide an alternative strategy for multinucleated cell–related diseases that involves restriction of mononucleated cell multinucleation through a spatiotemporally selective delivery system. A spatiotemporally selective delivery system restricts osteoclast multinucleation by posttranscriptional regulation.
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影响因子：
6.2
作者：
Chiu, Ya-Hui;Mensah, Kofi A.;Schwarz, Edward M.;Ju, Yawen;Takahata, Masahiko;Feng, Changyong;McMahon, Loralee A.;Hicks, David G.;Panepento, Ben;Keng, Peter C.;Ritchlin, Christopher T.
通讯作者：
Ritchlin, Christopher T.
DOI：
10.1056/nejmoa1916525
发表时间：
2020-08-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.9
作者：
Enuka Y;Lauriola M;Feldman ME;Sas-Chen A;Ulitsky I;Yarden Y
通讯作者：
Yarden Y
影响因子：
8
作者：
Cai, Wei;Dai, Xuejiao;Chen, Jun
通讯作者：
Chen, Jun
DOI：
10.1073/pnas.64.2.536
发表时间：
1969-01-01
影响因子：
11.1
作者：
BRATT, MA;GALLAHER, WR
通讯作者：
GALLAHER, WR