Nano-hydroxyapatite modulates osteoblast lineage commitment by stimulation of DNA methylation and regulation of gene expression.
Nano-hydroxyapatite modulates osteoblast lineage commitment by stimulation of DNA methylation and regulation of gene expression.
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DOI：
10.1016/j.biomaterials.2015.06.039
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发表时间：
2015-10
期刊：
影响因子：
14
通讯作者：
Beck GR Jr
中科院分区：
文献类型：
--
作者：
Ha SW;Jang HL;Nam KT;Beck GR Jr
羟基磷灰石（HA）是骨骼和牙列的主要结构成分。在生物条件下，透明质酸不会自发产生，因此必须通过矿化细胞（如成骨细胞）积极合成。透明质酸由细胞主动合成并沉积形成矿化基质的机制尚不完全清楚，而矿化对细胞功能的影响则更不清楚。透明质酸可以化学合成（HAp），因此目前正在研究作为一种有前途的治疗性生物材料，用作骨骼修复和牙科应用的功能性支架和种植涂层。本文研究了纳米hap （10×100 nm）对成骨细胞谱系承诺和分化的生物学效应。暴露于早期分化成骨细胞导致基因表达的显著和持续变化，增加和减少，而后期成骨细胞的反应要弱得多。对启动子区（最敏感的基因之一）碱性磷酸酶的分析发现，细胞暴露于纳米hap后，DNA甲基化受到刺激。总的来说，这些结果揭示了纳米hap对细胞功能的新表观遗传调控，这对谱系测定和纳米材料的新潜在治疗用途具有重要意义。
Hydroxyapatite (HA) is the primary structural component of the skeleton and dentition. Under biological conditions, HA does not occur spontaneously and therefore must be actively synthesized by mineralizing cells such as osteoblasts. The mechanism(s) by which HA is actively synthesized by cells and deposited to create a mineralized matrix are not fully understood and the consequences of mineralization on cell function are even less well understood. HA can be chemically synthesized (HAp) and is therefore currently being investigated as a promising therapeutic biomaterial for use as a functional scaffold and implant coating for skeletal repair and dental applications. Here we investigated the biological effects of nano-HAp (10×100 nm) on the lineage commitment and differentiation of bone forming osteoblasts. Exposure of early stage differentiating osteoblasts resulted in dramatic and sustained changes in gene expression, both increased and decreased, whereas later stage osteoblasts were much less responsive. Analysis of the promoter region one of the most responsive genes, alkaline phosphatase, identified the stimulation of DNA methylation following cell exposure to nano-HAp. Collectively, the results reveal the novel epigenetic regulation of cell function by nano-HAp which has significant implication on lineage determination as well as identifying a novel potential therapeutic use of nanomaterials.