In vitro Models of Bone Remodelling and Associated Disorders.
In vitro Models of Bone Remodelling and Associated Disorders.
复制标题
骨骼重塑和相关疾病的体外模型。
DOI：
10.3389/fbioe.2018.00134
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发表时间：
2018
影响因子：
5.7
通讯作者：
Reilly GC
中科院分区：
文献类型：
--
作者：
Owen R;Reilly GC
骨质疏松等疾病破坏了骨的重建，导致成骨细胞的骨形成和破骨细胞的吸收之间的失衡。对这些代谢性骨骼疾病的研究主要是在体内进行的；然而，在过去的十年里，人们对建立能够减少或取代我们对动物试验的依赖的体外模型越来越感兴趣。随着生物材料和组织工程学的最新进展，基于实验室的替代物的可行性越来越大；然而，到目前为止，还没有建立体外骨重建的模型。在体内，重组是由成骨细胞和破骨细胞组成的有组织的包，称为骨多细胞单位(BMU)。破骨细胞是否形成和重塑的关键决定因素是RANKL和OPG之间的比例，RANKL是一种刺激破骨细胞生成的细胞因子，而OPG是一种抑制因子。本文首先详细介绍了调节RANKL/OPG比例的不同环境、条件和因素，以及要建立一个可靠的体外模型需要考虑的基本因素。随后，我们检查了到目前为止在使用三维共培养复制体外重塑方面所取得的成就，然后概述了这种系统已经如何用于相关疾病的研究，如转移性癌症和牙科疾病。最后，讨论了未来需要纳入的最重要的考虑因素。它详细说明了使用能够内源性产生所需细胞因子的细胞的必要性，机械刺激的应用，以及适当激素的存在，以产生一个健壮的骨重建模型。
Disruption of bone remodelling by diseases such as osteoporosis results in an imbalance between bone formation by osteoblasts and resorption by osteoclasts. Research into these metabolic bone disorders is primarily performed in vivo; however, in the last decade there has been increased interest in generating in vitro models that can reduce or replace our reliance on animal testing. With recent advances in biomaterials and tissue engineering the feasibility of laboratory-based alternatives is growing; however, to date there are no established in vitro models of bone remodelling. In vivo, remodelling is performed by organised packets of osteoblasts and osteoclasts called bone multicellular units (BMUs). The key determinant of whether osteoclasts form and remodelling occurs is the ratio between RANKL, a cytokine which stimulates osteoclastogenesis, and OPG, its inhibitor. This review initially details the different circumstances, conditions, and factors which have been found to modulate the RANKL:OPG ratio, and fundamental factors to be considered if a robust in vitro model is to be developed. Following this, an examination of what has been achieved thus far in replicating remodelling in vitro using three-dimensional co-cultures is performed, before overviewing how such systems are already being utilised in the study of associated diseases, such as metastatic cancer and dental disorders. Finally, a discussion of the most important considerations to be incorporated going forward is presented. This details the need for the use of cells capable of endogenously producing the required cytokines, application of mechanical stimulation, and the presence of appropriate hormones in order to produce a robust model of bone remodelling.
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影响因子：
2.6
作者：
Basdra, EK;Komposch, G
通讯作者：
Komposch, G
影响因子：
9.7
作者：
Clarke, Mark S. F.;Sundaresan, Alamelu;Pellis, Neal R.
通讯作者：
Pellis, Neal R.
DOI：
10.1186/bcr2781
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Chen YC;Sosnoski DM;Mastro AM
通讯作者：
Mastro AM
影响因子：
6.2
作者：
Cai, Xiaofeng;Xing, Junjie;Humphrey, Mary Beth
通讯作者：
Humphrey, Mary Beth
影响因子：
3.3
作者：
Bubendorf, L;Schöpfer, A;Mihatsch, MJ
通讯作者：
Mihatsch, MJ