Ex Vivo Replication of Phenotypic Functions of Osteocytes through Biomimetic 3D Bone Tissue Construction
| Autor: | Ciaran Mannion, Yair D Kissin, Saba Choudhary, Qiaoling Sun, Woo Y. Lee, Jenny Zilberberg |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Histology Physiology Endocrinology Diabetes and Metabolism Parathyroid hormone Bone tissue Mechanotransduction Cellular Osteocytes Article Bone and Bones 03 medical and health sciences Biomimetics Internal medicine Bone cell medicine Humans Mechanotransduction Cells Cultured biology Chemistry Middle Aged In vitro Cell biology 030104 developmental biology Endocrinology medicine.anatomical_structure Phenotype RANKL Cancer cell Bone Morphogenetic Proteins biology.protein Ex vivo |
| Popis: | 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 20–25 μm 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. |
| Databáze: | OpenAIRE |
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