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Mg–Al and Zn–Al Layered Double Hydroxides Promote Dynamic Expression of Marker Genes in Osteogenic Differentiation by Modulating Mitogen‐Activated Protein Kinases
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2017-12-27 , DOI: 10.1002/adhm.201700693
Ha Ram Kang 1 , Célio Junior da Costa Fernandes 1 , Rodrigo Augusto da Silva 1 , Vera Regina Leopoldo Constantino 2 , Ivan Hong Jun Koh 3 , Willian F. Zambuzzi 1
Affiliation  

The effect of LDH samples comprised of chloride anions intercalated between positive layers of magnesium/aluminum (Mg‐Al LDH) or zinc/aluminum (Zn‐Al LDH) chemical composition on pre‐osteoblast performance is investigated. Non‐cytotoxic concentrations of both LDHs modulated pre‐osteoblast adhesion by triggering cytoskeleton rearrangement dependent on recruiting of Cofilin, which is modulated by the inhibition of the Protein Phosphatase 2A (PP2A), culminating in osteoblast differentiation with a significant increase of osteogenic marker genes. The alkaline phosphatase (ALP) and bone sialoprotein (BSP) are significantly up‐modulated by both LDHs; however, Mg‐Al LDH nanomaterial promoted even more significance than both experimental controls, while the phosphorylations of mitogen‐activated protein kinase (MAPKs)‐ extracellular signal–regulated kinases (ERK) and c‐Jun N‐terminal kinase (JNK) significantly increased. MAPK signaling is necessary to activate Runt‐related transcription factor 2 (RUNX2) gene. Concomitantly, it is also investigated whether challenged osteoblasts are able to modulate osteoclastogenesis by investigating both osteoprotegerin (OPG) and Receptor activator of nuclear factor kappa‐ligand (RANKL) in this model; a dynamic reprogramming of both these genes is found, suggesting LDHs in modulating osteoclastogenesis. These results suggest that LDHs interfere in bone remodeling, and they can be considered as nanomaterials in graft‐based bone healing or drug‐delivery materials for bone disorders.

中文翻译:

Mg-Al和Zn-Al层状双氢氧化物通过调节丝分裂原活化的蛋白激酶促进成骨分化中标记基因的动态表达。

研究了由氯离子组成的LDH样品插入在镁/铝(Mg-Al LDH)或锌/铝(Zn-Al LDH)化学成分的正层之间对成骨细胞性能的影响。两种LDH的非细胞毒性浓度均通过触发依赖Cofilin募集的细胞骨架重排来调节成骨细胞前粘附,而Cofilin的抑制则受蛋白磷酸酶2A(PP2A)的抑制,最终导致成骨细胞分化并显着增加成骨标记基因。碱性磷酸酶(ALP)和骨涎蛋白(BSP))被两个LDH显着上调; 然而,Mg-Al LDH纳米材料比两个实验对照都具有更大的意义,而丝裂原激活的蛋白激酶(MAPKs),细胞外信号调节激酶(ERK)和c-Jun N端激酶(JNK)的磷酸化显着增加。MAPK信号是激活Runt相关转录因子2(RUNX2)基因所必需的。同时,还通过研究骨保护素(OPG)和核因子κ配体的受体激活剂(RANKL)来研究受攻击的成骨细胞是否能够调节破骨细胞生成。)在此模型中;发现这两个基因的动态重编程,表明LDHs在调节破骨细胞生成中。这些结果表明,LDHs干扰了骨骼的重塑,可以被认为是基于移植物的骨愈合或用于骨骼疾病的药物输送材料中的纳米材料。
更新日期:2017-12-27
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