Department of Materials Science and Chemical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA.
Department of Biomedical Engineering, Chemistry and Biological Sciences, Stevens Institute of Technology, Hoboken, NJ, USA.
Bone. 2018 Jan;106:148-155. doi: 10.1016/j.bone.2017.10.019. Epub 2017 Oct 21.
Osteocytes, residing as 3-dimensionally (3D) networked cells in bone, are well known to regulate bone and mineral homeostasis and have been recently implicated to interact with cancer cells to influence the progression of bone metastases. In this study, a bone tissue consisting of 3D-networked primary human osteocytes and MLO-A5 cells was constructed using: (1) the biomimetic close-packed assembly of 20-25μm microbeads with primary cells isolated from human bone samples and MLO-A5 cells and (2) subsequent perfusion culture in a microfluidic device. With this 3D tissue construction approach, we replicated ex vivo, for the first time, the mechanotransduction function of human primary osteocytes and MLO-A5 cells by correlating the effects of cyclic compression on down-regulated SOST and DKK1 expressions. Also, as an example of using our ex vivo model to evaluate therapeutic agents, we confirmed previously reported findings that parathyroid hormone (PTH) decreases SOST and increases the ratio of RANKL and OPG. In comparison to other in vitro models, our ex vivo model: (1) replicates the cell density, phenotype, and functions of primary human osteocytes and MLO-A5 cells and (2) thus provides a clinically relevant means of studying bone diseases and metastases.
成骨细胞作为三维（3D）网络细胞存在于骨骼中，其调节骨骼和矿物质稳态的功能已广为人知，最近的研究还表明成骨细胞与癌细胞相互作用，影响骨转移的进展。在这项研究中，通过以下两种方法构建了一种由三维网络原代人成骨细胞和 MLO-A5 细胞组成的骨组织：（1）使用仿生密堆积组装 20-25μm 微珠，将人骨样本分离的原代细胞和 MLO-A5 细胞进行组装；（2）随后在微流控装置中进行灌注培养。通过这种 3D 组织构建方法，我们首次在体外复制了人原代成骨细胞和 MLO-A5 细胞的机械转导功能，通过比较循环压缩对 SOST 和 DKK1 表达下调的影响。此外，作为使用我们的体外模型评估治疗剂的一个例子，我们证实了之前的研究结果，甲状旁腺激素（PTH）降低 SOST 并增加 RANKL 和 OPG 的比值。与其他体外模型相比，我们的体外模型：（1）复制了原代人成骨细胞和 MLO-A5 细胞的细胞密度、表型和功能；（2）因此为研究骨骼疾病和转移提供了一种具有临床相关性的方法。
