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Exercise is recommended to help maintain musculoskeletal health during treatment. As primary mechanosensors and regulators of bone homeostasis, osteocytes recently investigate for their roles in prostate cancer bone metastasis. Recently, in vivo studies show that exercise mitigates prostate tumor progression and preserves bone structure. In contrast, in vitro studies indicate direct prostate cancer\u2013osteocyte interactions under mechanical loading conditions promote prostate cancer growth and migration but exclude other host cells present in the metastatic bone microenvironment. Thus, these in vitro findings are not consistent with recent in vivo results. In this study, the role of mechanically stimulated osteocytes during the initial stages of metastatis in osteoblast\u2010rich areas is examined. When treated with conditioned media from flow\u2010stimulated osteocytes, osteoblasts reduce PC\u20103 wound healing migration and invasion compared to static controls. Of interest, osteoblasts treated with flow\u2010stimulated MLO\u2010Y4 and primary osteocyte conditioned media suppress PC\u20103 cancer cell growth, alter cancer cell morphology, and preserve mineralized matrix in a microfluidic co\u2010culture assay. Overall, the inhibitory role of mechanical loading of osteocytes on the early\u2010stage metastasis of the endosteal surface during prostate cancer bone metastasis is demonstrated.<\/jats:p>","DOI":"10.1002\/adbi.202500379","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T12:31:06Z","timestamp":1762950666000},"source":"Crossref","is-referenced-by-count":2,"title":["Osteocytes under Mechanical Loading Regulate PC\u20103 Cancer Cell\u2013Mineral Interactions during Early\u2010Stage Metastasis to Bone"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9797-8530","authenticated-orcid":false,"given":"Kimberly","family":"Seaman","sequence":"first","affiliation":[{"name":"Department of Mechanical and Industrial Engineering University of Toronto  Toronto Ontario M5S 3G8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cell &amp; Systems Biology University of Toronto  Toronto Ontario M5S 3G5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Du","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto Ontario M4N 3M5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burton","family":"Yang","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto Ontario M4N 3M5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Industrial Engineering University of Toronto  Toronto Ontario M5S 3G8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8889-4173","authenticated-orcid":false,"given":"Lidan","family":"You","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Industrial Engineering University of Toronto  Toronto Ontario M5S 3G8 Canada"},{"name":"Department of Mechanical and Materials Engineering Queen's University  Kingston Ontario K7L 3N6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22742"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2020.09.006"},{"key":"e_1_2_9_3_1","first-page":"1832","volume":"62","author":"Taichman R. 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