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  1. Research Research
  2. Influence of Mechanosensitive Ion Channels on Chondrocytes under various Gravitational Loads Influence of Mechanosensitive Ion Channels on Chondrocytes under various Gravitational Loads

Influence of Mechanosensitive Ion Channels on Chondrocytes under various Gravitational Loads

Can chondrocyte dedifferentiation be modulated under simulated microgravity by using the Random Positioning Machine? Do mechanosensitive ion channels, such as Transient Receptor Potential ion channels, play a significant role in the dedifferentiation process?

Brief information

School:

Engineering and Architecture

Status:

Completed

Period:

01.01.2014 - 31.12.2016

Overview

Disuse or prolonged mechanical unloading of cartilage leads to accelerated degeneration. This is especially of concern for bed-ridden patients and astronauts while in space. Because cartilage has limited capacity for self-repair, restoration of damaged or degenerated cartilage remains a major clinical issue. Cell based tissue engineering approaches are limited since chondrocytes tend to dedifferentiate in vitro (especially 2D) culture. Thereby they lose the ability to produce high quality cartilage.

Because cartilage and chondrocytes are highly mechanosensitive, several experiments were performed under real and simulated microgravity to investigate the responses to a mechanically unloaded environment. The intervertebral disc (IVD) of rats flown in space showed clear signs of disc degeneration: The wet and dry weights were reduced and the collagen to proteoglycan ratio was increased. Similar effects were seen under simulated microgravity generated by clinostat rotation. A cell experiment performed under real microgravity aboard the International Space Station (ISS) and under simulated microgravity using a Random Positioning Machine (RPM) showed a reduced deposition of proteoglycans and reduced cellular density. However the gene expression ratio of collagen I/II were lower in the ISS and RPM samples, compared to the static control. Decreased collagen I/II ratio was later confirmed in two experiments under simulated microgravity using the RPM. These data suggest that mechanical unloading created either by space exposure or by simulation enhances signs for degeneration but at the same time retard phenotype dedifferentiation. The conversion of mechanical force into an intracellular signal has not been fully elucidated and thus it is still not clear what mechanisms are responsible for the response of cartilage and chondrocytes to either real or simulated microgravity.

Some Transient Receptor Potential (TRP) channels are well known for their mechanosenitivity and are therefore of central interest. Studies have shown that chondrocytes dedifferentiation in 2D culture lead to an altered gene expression of several members of the TRP family. While the function of most TRP channels in chondrocytes remains unknown, TRPV4 showed to play an important role in the volume regulation of chondrocytes exposed to osmotic challenges.

The aim of this project is to investigate if the Random Positioning Machine (RPM) can be used to modulate chondrocyte dedifferentiation and if Transient Receptor Potential (TRP) ion channelsplay a significant role in this dedifferentiation process.

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Facts

Type of project

Forschung

Internal organisations involved
  • CC Bioscience and Medical Engineering
Funding
  • andere
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Persons involved: internal

Project manager
  • Simon Wüest
Member of project team
  • Marcel Egli
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Persons involved: external

External member of project team
  • Benjamin Gantenbein

Publications

  • Article, review; peer reviewed (3)

    • Wüest, Simon; Rösch, Christian; Ille, Fabian & Egli, Marcel (2017). Calcium dependent current recordings in Xenopus laevis oocytes in microgravity. Acta Astronautica, 141, 228-236. doi: https://doi.org/10.1016/j.actaastro.2017.10.003

    • Wüest, Simon; Stern, Philip; Casartelli, Ernesto & Egli, Marcel (2017). Fluid Dynamics Appearing during Simulated Microgravity Using Random Positioning Machines. PLOS ONE, 1-19. doi: https://doi.org/10.1371/journal.pone.0170826

    • Wüest, Simon; Richard, Stéphane; Kopp, Sascha; Grimm, Daniela & Egli, Marcel (2015). Simulated Microgravity: Critical Review on the Use of Random Positioning Machines for Mammalian Cell Culture. BioMed Research International, 2015(Article ID 971474), 2-8.

  • Report/working paper (1)

    • Egli, Marcel; Richard, Stéphane & Wüest, Simon (2014). A Novel Microgravity Simulator Applicable for Three-Dimensional Cell Culturing (Microgravity Science and Technology).

Brief information

School:

Engineering and Architecture

Status:

Completed

Period:

01/01/2014 - 12/31/2016

Project Head

Dr. Simon Wüest

Senior Research Associate

+41 41 349 36 23

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