An In Vitro Bone Model to Investigate the Role of Triggering Receptor Expressed on Myeloid Cells-2 in Bone Homeostasis.

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  • Additional Information
    • Source:
      Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 101466663 Publication Model: Print Cited Medium: Internet ISSN: 1937-3392 (Electronic) Linking ISSN: 19373384 NLM ISO Abbreviation: Tissue Eng Part C Methods Subsets: MEDLINE
    • Publication Information:
      Original Publication: New Rochelle, NY : Mary Ann Liebert, Inc.
    • Subject Terms:
      Homeostasis* ; Models, Biological* ; Tissue Engineering*; Bone and Bones/*cytology ; Membrane Glycoproteins/*metabolism ; Osteoclasts/*cytology ; Receptors, Immunologic/*metabolism; Bone and Bones/metabolism ; Cells, Cultured ; Humans ; In Vitro Techniques ; Osteoclasts/metabolism
    • Abstract:
      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.
    • Contributed Indexing:
      Keywords: TREM-2; bone homeostasis; human progenitors; in vitro 3D model
    • Accession Number:
      0 (Membrane Glycoproteins)
      0 (Receptors, Immunologic)
      0 (TREM2 protein, human)
    • Publication Date:
      Date Created: 20180614 Date Completed: 20190313 Latest Revision: 20190313
    • Publication Date:
      20240513
    • Accession Number:
      10.1089/ten.TEC.2018.0061
    • Accession Number:
      29897015