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Status: Bibliographieeintrag

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Verfasst von:Lückgen, Janine [VerfasserIn]   i
 Diederichs, Solvig [VerfasserIn]   i
 Raqué, Elisabeth [VerfasserIn]   i
 Renkawitz, Tobias [VerfasserIn]   i
 Richter, Wiltrud [VerfasserIn]   i
 Buchert, Justyna [VerfasserIn]   i
Titel:Mechanoinduction of PTHrP/cAMP-signaling governs proteoglycan production in mesenchymal stromal cell-derived neocartilage
Verf.angabe:Janine Lückgen, Solvig Diederichs, Elisabeth Raqué, Tobias Renkawitz, Wiltrud Richter, Justyna Buchert
E-Jahr:2024
Jahr:December 2024
Umfang:11 S.
Illustrationen:Illustrationen
Fussnoten:Veröffentlicht: 05 September 2024 ; Gesehen am 05.02.2025
Titel Quelle:Enthalten in: Journal of cellular physiology
Ort Quelle:New York, NY [u.a.] : Wiley-Liss, 1932
Jahr Quelle:2024
Band/Heft Quelle:239(2024), 12 vom: Dez., Artikel-ID e31430, Seite 1-11
ISSN Quelle:1097-4652
Abstract:Abnormal mechanical loading is one of the major risk factors for articular cartilage degeneration. Engineered mesenchymal stromal cell (MSC)-derived cartilage holds great promise for cell-based cartilage repair. However, physiological loading protocols were shown to reduce matrix synthesis of MSC-derived neocartilage in vitro and the regulators of this undesired mechanoresponse remain poorly understood. Parathyroid hormone-related protein (PTHrP) is involved in cartilage development and can affect extracellular matrix (ECM) production during MSC chondrogenesis opposingly, depending on a continuous or transient exposure. PTHrP is induced by various mechanical cues in multiple tissues and species; but whether PTHrP is regulated in response to loading of human engineered neocartilage and may affect matrix synthesis in a positive or negative manner is unknown. The aim of this study was to investigate whether dynamic loading adjusts PTHrP-signaling in human MSC-derived neocartilage and whether it regulates matrix synthesis and other factors involved in the MSC mechanoresponse. Interestingly, MSC-derived chondrocytes significantly upregulated PTHrP mRNA (PTHLH) expression along with its second messenger cAMP in response to loading in our custom-built bioreactor. Exogenous PTHrP(1-34) induced the expression of known mechanoresponse genes (FOS, FOSB, BMP6) and significantly decreased glycosaminoglycan (GAG) and collagen synthesis similar to loading. The adenylate-cyclase inhibitor MDL-12,330A rescued the load-mediated decrease in GAG synthesis, indicating a direct involvement of cAMP-signaling in the reduction of ECM production. According to COL2A1-corrected hypertrophy-associated marker expression, load and PTHrP treatment shared the ability to reduce expression of MEF2C and PTH1R. In conclusion, the data demonstrate a significant mechanoinduction of PTHLH and a negative contribution of the PTHrP-cAMP signaling axis to GAG synthesis in MSC-derived chondrocytes after loading. To improve ECM synthesis and the mechanocompetence of load-exposed neocartilage, inhibition of PTHrP activity should be considered for MSC-based cartilage regeneration strategies.
DOI:doi:10.1002/jcp.31430
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.1002/jcp.31430
 kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.31430
 DOI: https://doi.org/10.1002/jcp.31430
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:cellular mechanotransduction
 chondrocytes
 mesenchymal stromal cells
 parathyroid hormone-related protein
 tissue engineering
K10plus-PPN:1916396453
Verknüpfungen:→ Zeitschrift

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