The role of Alk-1 and Alk-5 in the mechanosensing of chondrocytes

Cellular & Molecular Biology Letters

Patricia Sanz-Ramos²  Javier Dotor¹  Iñigo Izal-Azcárate² 

[1] DIGNA Biotech, Pamplona, Spain$$;Laboratory for Orthopaedic Research, University of Navarra, School of Medicine, Pamplona, Spain$$

关键词: Chondrocyte;    Mechanosensing;    Mechanobiology;    Mechanotransduction;    Collagen hydrogels;    TGFβ;    Differentiation;    Signalling;    Cartilage;    Chondrogenesis;   

DOI  :  10.2478/s11658-014-0220-6

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

We aim to demonstrate the role of Alk receptors in the response of hydrogel expansion. Chondrocytes from rat knees were cultured onto plastic and hydrogel surfaces. Alk-1 and Alk-5 were overexpressed or silenced and the effects on cells during expansion were tested and confirmed using peptide inhibitors for TGFβ. Overexpression of Alk-5 and silencing of Alk-1 led to a loss of the chondrocyte phenotype, proving that they are key regulators of chondrocyte mechanosensing. An analysis of the gene expression profile during the expansion of these modified cartilage cells in plastic showed a better maintenance of the chondrocyte phenotype, at least during the first passages. These passages were also assayed in a mouse model of intramuscular chondrogenesis. Our findings indicate that these two receptors are important mediators in the response of chondrocytes to changes in the mechanical environment, making them suitable targets for modulating chondrogenesis. Inhibition of TGFβ could also be effective in improving chondrocyte activity in aged or expanded cells that overexpress Alk-1.

【 授权许可】

Unknown