title: The role of Alk-1 and Alk-5 in the mechanosensing of chondrocytes.
abstract: 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.
authors.affiliation: Laboratory for Orthopaedic Research, University of Navarra, School of Medicine, Pamplona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sanz-Ramos
authors.forename: Javier
authors.initials: J
authors.lastname: Dotor
authors.forename: Iñigo
authors.initials: I
authors.lastname: Izal-Azcárate
mesh_terms: D029404:Activin Receptors / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology* / Q000637:transplantation; D003470:Culture Media / Q000737:chemistry; D019175:DNA Methylation; D015870:Gene Expression; D020100:Hydrogels / Q000737:chemistry; D040542:Mechanotransduction, Cellular; D008819:Mice, Nude; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D017208:Rats, Wistar; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C526764:Acvrl1 protein, rat; D003470:Culture Media; D020100:Hydrogels; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625842:Tgfbr1 protein, mouse; C000625843:Tgfbr1 protein, rat