Inverse regulation of cartilage neogenesis at physiologically relevant calcium conditions by human articular chondrocytes and mesenchymal stromal cells

• Verfasst von: Hammersen, Tim [VerfasserIn]
• Verfasst von: Buchert, Justyna [VerfasserIn]
• Verfasst von: Zietzschmann, Severin [VerfasserIn]
• Verfasst von: Diederichs, Solvig [VerfasserIn]
• Verfasst von: Richter, Wiltrud [VerfasserIn]
• Titel: Inverse regulation of cartilage neogenesis at physiologically relevant calcium conditions by human articular chondrocytes and mesenchymal stromal cells
• Verf.angabe: Tim Hammersen, Justyna Buchert, Severin Zietzschmann, Solvig Diederichs and Wiltrud Richter
• E-Jahr: 2023
• Jahr: 18 June 2023
• Umfang: 18 S.
• Fussnoten: Gesehen am 16.08.2023
• Titel Quelle: Enthalten in: Cells
• Ort Quelle: Basel : MDPI, 2012
• Jahr Quelle: 2023
• Band/Heft Quelle: 12(2023), 12, Artikel-ID 1659, Seite 1-18
• ISSN Quelle: 2073-4409
• DOI: doi:10.3390/cells12121659
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: chondrogenesis
• Sach-SW: extracellular matrix
• Sach-SW: parathyroid hormone-related peptide
• Sach-SW: stem cells
• Sach-SW: tissue engineering
• K10plus-PPN: 1856321274

Abstract

Elaborate bioreactor cultivation or expensive growth factor supplementation can enhance extracellular matrix production in engineered neocartilage to provide sufficient mechanical resistance. We here investigated whether raising extracellular calcium levels in chondrogenic cultures to physiologically relevant levels would provide a simple and inexpensive alternative to enhance cartilage neogenesis from human articular chondrocytes (AC) or bone marrow-derived mesenchymal stromal cells (BMSC). Interestingly, AC and BMSC-derived chondrocytes showed an opposite response to a calcium increase from 1.8 mM to 8 mM by which glycosaminoglycan (GAG) and collagen type II production were elevated during BMSC chondrogenesis but depressed in AC, leading to two-fold higher GAG/DNA values in BMSC-based neocartilage compared to the AC group. According to control treatments with Mg2+ or sucrose, these effects were specific for CaCl2 rather than divalent cations or osmolarity. Importantly, undesired pro-hypertrophic traits were not stimulated by calcium treatment. Specific induction of PTHrP mRNA and protein by 8.0mM calcium only in AC, along with negative effects of recombinant PTHrP1-34 on cartilage matrix production, suggested that the PTHrP pathway contributed to the detrimental effects in AC-based neocartilage. Altogether, raising extracellular calcium levels was discovered as a novel, simple and inexpensive stimulator for BMSC-based cartilage neogenesis without the need for special bioreactors, whereas such conditions should be avoided for AC.