Effects of clodronate and alendronate on osteoclast and osteoblast co-cultures on silk-hydroxyapatite films
Effects of clodronate and alendronate on osteoclast and osteoblast co-cultures on silk-hydroxyapatite films
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DOI：
10.1016/j.actbio.2013.09.028
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发表时间：
2014-01-01
影响因子：
9.7
通讯作者：
Kaplan, David L.
中科院分区：
文献类型：
--
作者：
Hayden, Rebecca S.;Vollrath, Moritz;Kaplan, David L.
本研究的目的是探讨骨质疏松相关治疗对体外骨重建的影响。该研究使用了之前建立的骨组织模拟系统，该系统由丝蛋白生物材料与羟基磷灰石和人类细胞组成。将丝羟基磷灰石膜与非含氮双膦酸盐氯膦酸盐或含氮双膦酸盐阿仑膦酸盐预复合，并与THP-1人急性单核细胞白血病细胞系衍生的破骨细胞、人间充质干细胞衍生的成骨细胞或两种细胞类型的直接共培养物一起培养。在12周内评估代谢活性、钙沉积和碱性磷酸酶活性，并评估重建的重塑生物材料表面的定量形态学变化。在由成骨细胞和成骨细胞与破骨细胞共培养物重塑的氯膦酸盐复合生物材料基质上发现代谢活性增加和粗糙度增加，即使剂量高到足以导致破骨细胞代谢活性降低90%。与低剂量阿仑膦酸钠复合的膜导致成骨细胞代谢活性和钙沉积增加，而较高剂量的破骨细胞、成骨细胞和共培养物中具有类似的毒性。这些结果指出了这些明确的骨模拟体外培养物作为骨相关疾病的治疗剂的有用筛选的实用性，特别是具有进行延长持续时间（这里为12周）的研究的能力，并且具有预复合药物以模拟体内发现的条件。(C)2013 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
The goal of this study was to explore the effects of osteoporosis-related therapeutics on bone remodeling in vitro. A previously established bone-tissue mimetic system consisting of silk protein biomaterials in combination with hydroxyapatite and human cells was used for the study. Silk-hydroxyapatite films were pre-complexed with the non-nitrogenous bisphosphonate clodronate or the nitrogenous bisphosphonate alendronate and cultured with THP-1 human acute monocytic leukemia cell line-derived osteoclasts, human mesenchymal stem cell derived osteoblasts or a direct co-culture of the two cell types. Metabolic activity, calcium deposition and alkaline phosphatase activity were assessed over 12 weeks, and reconstructed remodeled biomaterial surfaces were also evaluated for quantitative morphological changes. Increased metabolic activity and increased roughness were found on the clodronate-complexed biomaterial substrates remodeled by osteoblasts and co-cultures of osteoblasts with osteoclasts, even at doses high enough to cause a 90% decrease in osteoclast metabolic activity. Films complexed with low doses of alendronate resulted in increased metabolic activity and calcium deposition by osteoblasts, while higher doses were similarly toxic among osteoclasts, osteoblasts and co-cultures. These results point to the utility of these well-defined bone-mimetic in vitro cultures as useful screens for therapeutics for bone-related diseases, particularly with the ability to conduct studies for extended duration (here for 12 weeks) and with pre-complexed drugs to mimic conditions found in vivo. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.