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Verfasst von:Klampfleuthner, Felicia [VerfasserIn]   i
 Lotz, Benedict [VerfasserIn]   i
 Renkawitz, Tobias [VerfasserIn]   i
 Richter, Wiltrud [VerfasserIn]   i
 Diederichs, Solvig [VerfasserIn]   i
Titel:Stage-dependent activity and pro-chondrogenic function of PI3K/AKT during cartilage neogenesis from mesenchymal stromal cells
Verf.angabe:Felicia A.M. Klampfleuthner, Benedict Lotz, Tobias Renkawitz, Wiltrud Richter and Solvig Diederichs
E-Jahr:2022
Jahr:23 September 2022
Umfang:17 S.
Illustrationen:Illustrationen
Fussnoten:Gesehen am 09.12.2022
Titel Quelle:Enthalten in: Cells
Ort Quelle:Basel : MDPI, 2012
Jahr Quelle:2022
Band/Heft Quelle:11(2022), 19 vom: Sept., Artikel-ID 2965, Seite 1-17
ISSN Quelle:2073-4409
Abstract:Differentiating mesenchymal stromal cells (MSCs) into articular chondrocytes (ACs) for application in clinical cartilage regeneration requires a profound understanding of signaling pathways regulating stem cell chondrogenesis and hypertrophic degeneration. Classifying endochondral signals into drivers of chondrogenic speed versus hypertrophy, we here focused on insulin/insulin-like growth factor 1 (IGF1)-induced phosphoinositide 3-kinase (PI3K)/AKT signaling. Aware of its proliferative function during early but not late MSC chondrogenesis, we aimed to unravel the late pro-chondrogenic versus pro-hypertrophic PI3K/AKT role. PI3K/AKT activity in human MSC and AC chondrogenic 3D cultures was assessed via Western blot detection of phosphorylated AKT. The effects of PI3K inhibition with LY294002 on chondrogenesis and hypertrophy were assessed via histology, qPCR, the quantification of proteoglycans, and alkaline phosphatase activity. Being repressed by ACs, PI3K/AKT activity transiently rose in differentiating MSCs independent of TGFβ or endogenous BMP/WNT activity and climaxed around day 21. PI3K/AKT inhibition from day 21 on equally reduced chondrocyte and hypertrophy markers. Proving important for TGFβ-induced SMAD2 phosphorylation and SOX9 accumulation, PI3K/AKT activity was here identified as a required stage-dependent driver of chondrogenic speed but not of hypertrophy. Thus, future attempts to improve MSC chondrogenesis will depend on the adequate stimulation and upregulation of PI3K/AKT activity to generate high-quality cartilage from human MSCs.
DOI:doi:10.3390/cells11192965
URL:Volltext: https://doi.org/10.3390/cells11192965
 Volltext: https://www.mdpi.com/2073-4409/11/19/2965
 DOI: https://doi.org/10.3390/cells11192965
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:AKT
 cartilage
 chondrocyte hypertrophy
 chondrogenesis
 insulin
 LY294002
 mesenchymal stromal cells
 PI3K
 PKB
K10plus-PPN:182672687X
Verknüpfungen:→ Zeitschrift
 
 
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