Ceria nanoparticles enhance endochondral ossification-based critical-sized bone defect regeneration by promoting the hypertrophic differentiation of BMSCs via DHX15 activation
Ceria nanoparticles enhance endochondral ossification-based critical-sized bone defect regeneration by promoting the hypertrophic differentiation of BMSCs via DHX15 activation
复制标题
二氧化铈纳米粒子通过 DHX15 激活促进 BMSC 的肥大分化，从而增强基于软骨内骨化的临界尺寸骨缺损再生
DOI：
10.1096/fj.201802187r
复制
发表时间：
2019-05-01
期刊：
影响因子：
4.8
通讯作者：
Dong, Shiwu
中科院分区：
文献类型：
--
作者：
Li, Jianmei;Kang, Fei;Dong, Shiwu
中心性缺血坏死是传统组织工程骨修复骨缺损的最大障碍之一。由于其促进血管侵袭的能力，基于软骨内骨化的TEB已被应用于骨缺损再生。然而，在软骨内骨化过程中，软骨细胞肥大不足会阻碍血管浸润和基质矿化。鉴于最近的研究表明二氧化铈纳米颗粒（CNPs）改善了TEB内的血管分布，我们用CNPs修饰了TEB支架表面，并研究了CNPs对基于软骨内骨化的骨再生的影响和机制。在这项研究中使用的纳米粒子的合成微乳液法和阿仑膦酸钠锚定的聚乙二醇600改性。我们在皮下异位成骨模型和临界大小骨缺损小鼠模型中发现，CNP加速了新骨形成，增强了基于软骨内骨化的骨再生。从机制上讲，CNP通过激活RNA解旋酶DEAH（Asp-Glu-Ala-His）盒解旋酶15及其下游靶点p38 MAPK确保充分的肥大分化，显著促进基于软骨内骨化的骨再生。这些结果表明，CNP可用作生物材料，以提高临界尺寸骨缺损中基于软骨内骨化的骨再生的功效。Kang，F.，龚，X.，Bai，Y.，（1996年），美国，戴，J.，赵，C.，Dou，C.，曹志，Liang，M.，东河，巴西-地江，H.，杨，X.，Dong，S.二氧化铈纳米颗粒通过DHX 15激活促进BMSCs肥大分化增强基于软骨内骨化的临界尺寸骨缺损再生
Central ischemic necrosis is one of the biggest obstacles in the clinical application of traditional tissue-engineered bone (TEB) in critical-sized bone defect regeneration. Because of its ability to promote vascular invasion, endochondral ossification-based TEB has been applied for bone defect regeneration. However, inadequate chondrocyte hypertrophy can hinder vascular invasion and matrix mineralization during endochondral ossification. In light of recent studies suggesting that ceria nanoparticles (CNPs) improve the blood vessel distribution within TEB, we modified TEB scaffold surfaces with CNPs and investigated the effect and mechanism of CNPs on endochondral ossification-based bone regeneration. The CNPs used in this study were synthesized by the microemulsion method and modified with alendronate-anchored polyethylene glycol 600. We showed that CNPs accelerated new bone formation and enhanced endochondral ossification-based bone regeneration in both a subcutaneous ectopic osteogenesis model and a mouse model of critical-sized bone defects. Mechanistically, CNPs significantly promoted endochondral ossification-based bone regeneration by ensuring sufficient hypertrophic differentiation via the activation of the RNA helicase, DEAH (Asp-Glu-Ala-His) box helicase 15, and its downstream target, p38 MAPK. These results suggested that CNPs could be applied as a biomaterial to improve the efficacy of endochondral ossification-based bone regeneration in critical-sized bone defects.Li, J., Kang, F., Gong, X., Bai, Y., Dai, J., Zhao, C., Dou, C., Cao, Z., Liang, M., Dong, R., Jiang, H., Yang, X., Dong, S. Ceria nanoparticles enhance endochondral ossification-based critical-sized bone defect regeneration by promoting the hypertrophic differentiation of BMSCs via DHX15 activation.