Affiliations: [a] Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam – Universiteit van Amsterdam and Vrije Universiteit, Research Institute MOVE, Amsterdam, The Netherlands | [b] Dutch Experiment Support Center, Vrije Universiteit, Amsterdam, The Netherlands | [c] Department of Physics and Medical Technology, VU University Medical Center, Research Institute MOVE, Amsterdam, The Netherlands
Correspondence:
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Address for correspondence: Jenneke Klein-Nulend, Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam – Universiteit van Amsterdam and Vrije Universiteit, Research Institute MOVE, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Tel.: +31 20 4448660; Fax: +31 20 4448683; E-mail: j.kleinnulend@vumc.nl.
Abstract: Stochastic resonance is exhibited by many biological systems, where the response to a small stimulus is enhanced with the aid of noise. This intriguing possibility provides a novel paradigm for understanding previously reported osteogenic benefits of low amplitude dynamic loading. However, it is unknown whether bone cell mechanosensitivity is enhanced by noise as an alternative mechanism for an amplified response to small stresses. We studied whether noise of varying intensities enhanced the mechanosensitivity of MC3T3-E1 cells. Nitric oxide (NO) production was measured as the parameter for bone cell activation. Dynamic fluid shear stress stimulated bone cells provided an initial-stress kick was implemented. Without the initial stress-kick bone cells did not release a significant amount of NO demonstrating an essential non-linearity to bone cell responses to stress and the possibility of stochastic resonance in bone cell mechanosensitivity. The rapid NO response of MC3T3-E1 cells to a small periodic fluid shear stress was increased with the addition of noise compared to the response to stress with only noise. This confirms the possibility of stochastic resonance enhancement of NO production by bone cells. Since NO regulate bone formation as well as resorption, our results suggest that noise enhances the activity of bone cells in driving the mechanical adaptation of bone.
