Related Experiment Video
Updated: Apr 12, 2026
A Lab-On-A-Chip Platform for Stimulating Osteocyte Mechanotransduction and Analyzing Functional Outcomes of Bone Remodeling
Published on: May 21, 2020
Stiffness-sensitive gene regulation in human mesenchymal stem cells: Modelling mechanotransduction to predict
Jean-Philippe Berteau1, Abdennasser Chekroun2, Laurent Pujo-Menjouet3
1Department of Physical Therapy, College of Staten Island, City University of New York, 2800 Victory Blvd, Staten Island, NY, 10314, USA; New York Center for Biomedical Engineering, City College of New York, City University of New York, 160 Convent Ave, New York, NY, 10031, USA; Nanoscience Initiative, Advance Science Research Center, City University of New York, 85 St Nicholas Terrace, New York, NY, 10031, USA.
Abstract:
The goal of our study was to establish how a specific part of the bone Gene Regulatory Network (GRN) controls mineralization in response to stiffness. We hypothesized that a system of differential equations model stiffness-sensitive gene regulation in human mesenchymal stem cells through the epistatic genetic interactions between stiffness (e.g. WNT-β catenin pathway) and five of the main transcription factors and bone proteins (e.g. RUNX2, BSP, OSX, OC, and OPN). To test this hypothesis, we (i) performed in-vitro experiments culturing bone cells on different stiffness, (i) adapted our previously published model from being continuously time-dependent to continuously stiffness-sensitive, and (iii) simulated protein production in function of stiffness and other protein production from the best estimate of parameters coming from the experimental work. Our experimental findings reveal a non-parametric relationship between stiffness and RUNX2 production, with no discernible linear trends for other proteins. Modeling results demonstrate that continuous variations in stiffness enable simulation of bone GRN gene expression, fitting our novel experimental dataset. Specifically, our computational results indicate that OPN production peaks at low stiffness (8 kPa), while RUNX2, OSX, and OC achieve maximum production at higher stiffness levels (64 kPa). This alignment underscores the model's capacity to replicate experimental data accurately. Additionally, our approach predicts that WNT-β-catenin activation serves as an enhancer for OPN and BSP production. The model also highlights a negative feedback-like interaction between OC and BSP production. Stiffness variations were shown to have a significant impact on OC and BSP production and a moderate effect on OPN production. By employing a stiffness-sensitive gene regulation model, we provide insights into one of the mineralization patterns through the prediction of bone protein expression dynamics.
