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The role played by osteoclasts in such interactions is especially obscure. A modular human three\u2010dimensional (3D) in vitro bone niche model was developedThe model integrates osteoblasts and osteoclasts within a mineralized scaffold, recreating an endosteal\u2010like microenvironment for co\u2010culture with PCa cell lines and patient\u2010derived organoids (PDOs). The engineered construct maintains osteoblastic differentiation and supports osteoclastogenesis, confirmed by lineage markers including osteocalcin, osteopontin (OPN), and tartrate\u2010resistant acid phosphatase (TRAP). Co\u2010culture with PCa cells downregulates osteoblast\u2010 and osteoclast\u2010associated genes (IBSP, OPN, TRAP) in bone cells, suggesting tumor\u2010mediated suppression of bone remodeling. Conversely, co\u2010cultured PCa cells exhibit niche\u2010dependent osteomimicry, characterized by upregulation of osteoblastic (SPARC, BGLAP) and osteoclastic (TRAP) markers and strongly regulated by the presence of osteoclasts. The platform also supports engraftment and proliferation of PDOs without exogenous PCa\u2010specific growth factors, underscoring its translational relevance. This osteoblastic\u2010osteoclastic niche model provides a human system that captures PCa\u2010bone cell interactions in a clinically relevant context, with potential utility for mechanistic and translational studies.<\/jats:p>","DOI":"10.1002\/adhm.202505893","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:27:13Z","timestamp":1781238433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Fully Human Engineered Bone Niche With Endogenous Osteoclastogenesis Reveals Osteoclast\u2010Dependent Osteomimicry in Prostate Cancer Cells"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1486-8011","authenticated-orcid":false,"given":"Andrea","family":"Mazzoleni","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Basel  Basel Switzerland"},{"name":"Department of Biomedicine University of Basel and 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