AnIn VitroBone Model to Investigate the Role of Triggering Receptor Expressed on Myeloid Cells-2 in Bone Homeostasis

细胞生物学 化学 骨吸收 骨髓 受体 骨重建 平衡 祖细胞 骨细胞 免疫学 内分泌学 干细胞 生物 生物化学
作者
Eleonora Rossi,Éva Mracskó,Adam Papadimitropoulos,Nima Allafi,Dieter P. Reinhardt,Arne Mehrkens,Iván Martín,Irène Knuesel,Arnaud Scherberich
出处
期刊:Tissue Engineering Part C-methods [Mary Ann Liebert]
卷期号:24 (7): 391-398 被引量:9
标识
DOI:10.1089/ten.tec.2018.0061
摘要

Triggering receptor expressed on myeloid cells-2 (TREM-2), a transmembrane receptor expressed by macrophages, microglia, and osteoclasts (OCs), plays a protective role in late-onset Alzheimer Disease (AD). To validate TREM-2 as a therapeutic target in AD, its potential secondary parallel effect on bone homeostasis should be clarified. However, animal models and monolayer cultures of human cells were shown poorly predictive of TREM-2 function in human. Therefore, this study aimed to engineer a tridimensional in vitro model using human progenitors differentiated into osteoblasts and OCs, recapitulating physiological bone homeostasis. Human bone marrow-derived mesenchymal cells were seeded and cultured under perfusion inside a collagen type I scaffold for 3 weeks, generating osteoblasts and mineralized matrix. Human peripheral blood-derived CD14+ monocytes were subsequently seeded through the generated tissue, thanks to perfusion flow, and further cultured for up to 3 weeks with an inductive medium, generating mature OCs. This culture system supported collagenous matrix deposition and resorption, allowing for the investigation of kinetic of soluble TREM-2 over the coculture time. Agonistic activation of TREM-2 in this model had no effect on OC activity or on mineralized matrix turnover. In conclusion, the engineered culture system represents a tridimensional, in vitro human bone model for drug testing and suggested no effect of TREM-2 agonist on bone resorption.
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