Influence of Mechanical Unloading on Articular Chondrocyte Dedifferentiation.

Wüest, Simon; Calió, Martina; Wernas, Timon; Tanner, Samuel; Giger-Lange, Christina; Wyss, Fabienne; Ille, Fabian; Gantenbein, Benjamin; Egli, Marcel (2018). Influence of Mechanical Unloading on Articular Chondrocyte Dedifferentiation. International journal of molecular sciences, 19(5) Molecular Diversity Preservation International MDPI 10.3390/ijms19051289

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Due to the limited self-repair capacity of articular cartilage, the surgical restoration of defective cartilage remains a major clinical challenge. The cell-based approach, which is known as autologous chondrocyte transplantation (ACT), has limited success, presumably because the chondrocytes acquire a fibroblast-like phenotype in monolayer culture. This unwanted dedifferentiation process is typically addressed by using three-dimensional scaffolds, pellet culture, and/or the application of exogenous factors. Alternative mechanical unloading approaches are suggested to be beneficial in preserving the chondrocyte phenotype. In this study, we examined if the random positioning machine (RPM) could be used to expand chondrocytes in vitro such that they maintain their phenotype. Bovine chondrocytes were exposed to (a) eight days in static monolayer culture; (b) two days in static monolayer culture, followed by six days of RPM exposure; and, (c) eight days of RPM exposure. Furthermore, the experiment was also conducted with the application of 20 mM gadolinium, which is a nonspecific ion-channel blocker. The results revealed that the chondrocyte phenotype is preserved when chondrocytes go into suspension and aggregate to cell clusters. Exposure to RPM rotation alone does not preserve the chondrocyte phenotype. Interestingly, the gene expression (mRNA) of the mechanosensitive ion channel decreased with progressing dedifferentiation. In contrast, the gene expression (mRNA) of the mechanosensitive ion channel was reduced around fivefold to 10-fold in all of the conditions. The application of gadolinium had only a minor influence on the results. This and previous studies suggest that the chondrocyte phenotype is preserved if cells maintain a round morphology and that the ion channel could play a key role in the dedifferentiation process.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute for Surgical Technology & Biomechanics ISTB

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Wüest, Simon; Calió, Martina and Gantenbein, Benjamin

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1661-6596

Publisher:

Molecular Diversity Preservation International MDPI

Language:

English

Submitter:

Benjamin Gantenbein

Date Deposited:

30 Apr 2018 12:42

Last Modified:

24 Oct 2019 10:33

Publisher DOI:

10.3390/ijms19051289

PubMed ID:

29693628

Uncontrolled Keywords:

TRPC1 TRPV4 articular chondrocytes bovine primary cells dedifferentiation mechanosensitive ion channel qPCR random positioning machine (RPM) simulated microgravity

BORIS DOI:

10.7892/boris.116177

URI:

https://boris.unibe.ch/id/eprint/116177

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