---
title: "3D Perfused Osteocyte Platform Shows Subtype- and Radiation-Dependent Loss of Mechanotransduction"
id: "biorxiv-6-novel-3d-mature-osteocyte-perfusion-platform-reveals-subtype-dependent-and"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-6-novel-3d-mature-osteocyte-perfusion-platform-reveals-subtype-dependent-and"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.22.760275v1?rss=1"
published_at: "2026-10-23T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# 3D Perfused Osteocyte Platform Shows Subtype- and Radiation-Dependent Loss of Mechanotransduction
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-6-novel-3d-mature-osteocyte-perfusion-platform-reveals-subtype-dependent-and
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.22.760275v1?rss=1)
- **Published At:** 2026-10-23T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Investigators developed a physiologically relevant 3D mineralized scaffold with forced perfusion to culture mature, dendrite-bearing **osteocytes** for mechanobiology studies. - The platform was optimized for perfusion and validated by flow-induced suppression of **Sost**, and by responsiveness to parathyroid hormone, indicating functional mechanosensing. - Conditioned media (CM) from estrogen receptor–positive (ER+) ZR-75-1 and triple-negative (TN) MDA-MB-231 breast cancer cells were collected 24 hours after 0 or 2 Gy irradiation and applied to 3D osteocytes. - Downstream osteocyte gene expression endpoints included Sost, Tnfsf11 (encoding **RANKL**), and Tnfrsf11b; these transcriptional readouts were used to assess mechanoresponsiveness after flow. - Non-irradiated ER+ CM preserved flow-induced suppression of **Sost**, but ER+ CM from cells receiving 2 Gy radiation abolished that suppression. - TN CM blunted flow-induced **Sost** suppression regardless of irradiation status, indicating subtype-dependent secretome effects on osteocyte mechanotransduction. - Proteomic profiling (84 oncology targets) showed BCa subtype as the dominant determinant of secretome composition; 2 Gy radiation produced directional changes in secretomes that differed by subtype. - Authors noted that low-dose radiation further exacerbates secretome-mediated mechanosensory loss in ER+ disease, identifying tumor-derived targets for potential skeletal-restorative strategies. - The study presented a new in vitro platform to interrogate tumor–osteocyte crosstalk but remains a preprint and has not undergone peer review.
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Antonio Salcido-Alcántar Jr. 1 University of Colorado Boulder; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Antonio%2BSalcido-Alc%C3%A1ntar%2B%3Cspan%2Bclass%3D%22nlm-suffix%22%3EJr.%3C/span%3E "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Salcido-Alc%C3%A1ntar%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAntonio%2BSalcido-Alc%25C3%25A1ntar%2BJr.) Corrin Bowman 1 University of Colorado Boulder; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Corrin%2BBowman%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Bowman%20C&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ACorrin%2BBowman%2B) Elaine Goldman 1 University of Colorado Boulder; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Elaine%2BGoldman%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Goldman%20E&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AElaine%2BGoldman%2B) Emma N Briggs 1 University of Colorado Boulder; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Emma%2BN%2BBriggs%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Briggs%20EN&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AEmma%2BN%2BBriggs%2B) Anthony M Bierschenk 1 University of Colorado Boulder; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Anthony%2BM%2BBierschenk%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Bierschenk%20AM&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAnthony%2BM%2BBierschenk%2B) Tanvi K Rami 1 University of Colorado Boulder; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Tanvi%2BK%2BRami%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Rami%20TK&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ATanvi%2BK%2BRami%2B) William Roy Thompson 2 Indiana University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=William%2BRoy%2BThompson%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Thompson%20WR&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AWilliam%2BRoy%2BThompson%2B) * [ORCID record for William Roy Thompson](http://orcid.org/0000-0002-7022-585X "Open in new tab") Maureen E Lynch 3 University of Colorado at Boulder * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Maureen%2BE%2BLynch%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Lynch%20ME&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMaureen%2BE%2BLynch%2B) * [ORCID record for Maureen E Lynch](http://orcid.org/0000-0002-8247-2073 "Open in new tab") * For correspondence: maureen.lynch@colorado.edu * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.22.760275v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5898061/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.22.760275v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5898061/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.22.760275v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5898061/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.10.22.760275v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5898061/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.22.760275v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5898061/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Osteocytes (OCys) coordinate bone remodeling by transducing mechanical signals into anabolic cues, primarily through suppressing sclerostin and RANKL. In breast cancer (BCa) bone metastasis, mechanical loading fails to restore lost bone, pointing to tumor-induced OCy mechanosensory dysfunction. Here, we investigate how BCa molecular subtype heterogeneity and frontline therapies like radiation influence OCy mechanobiology. We leveraged a 3D mineralized scaffold paired with a forced perfusion bioreactor to establish a physiologically relevant model of mature, dendrite-bearing OCys. After optimizing perfusion parameters, 3D mature OCys were exposed to conditioned media (CM) from estrogen receptor-positive (ER+; ZR-75-1) or triple-negative (TN; MDA-MB-231) BCa cells generated 24 h post-irradiation (0 vs. 2 Gy). Downstream OCy gene expression (Sost, Tnfsf11, Tnfrsf11b) and tumor CM proteomic profiles (84 oncology targets) were evaluated. Differentiated 3D MPC-2s exhibited interconnected dendritic networks, classical responsiveness to parathyroid hormone, and robust flow-induced Sost suppression. Non-irradiated ER+ BCa CM preserved canonical OCy mechanoresponsiveness (Sost downregulation post-flow), but this response was eliminated when ER+ cells received 2 Gy radiation. Conversely, TN CM blunted flow-induced Sost suppression regardless of irradiation status. Proteomic profiling revealed that BCa subtype was the primary driver of secretome composition, whereas 2 Gy radiation induced distinct directional secretome shifts between subtypes. These findings demonstrate that BCa-induced impairment of OCy mechanosensing is subtype-dependent and that low-dose radiation further exacerbates secretome-mediated mechanosensory loss in ER+ disease, highlighting key tumor-derived targets for restoring skeletal health. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared U.S. National Science Foundation, BMMB-2047187 National Institutes of Health, T32AR080630 University of Colorado Boulder, 9866 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY 4.0 International license](http://creativecommons.org/licenses/by/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.10.22.760275v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/23/2026.10.22.760275.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.10.22.760275v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Novel 3D Mature Osteocyte Perfusion Platform Reveals Subtype-Dependent and Radiation-Sensitive Disruption of Mechanotransduction by Breast Cancer Secretomes Antonio Salcido-Alcántar Jr., Corrin Bowman, Elaine Goldman, Emma N Briggs, Anthony M Bierschenk, Tanvi K Rami, William Roy Thompson, Maureen E Lynch bioRxiv 2026.10.22.760275; doi: https://doi.org/10.64898/2026.10.22.760275 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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