Comparative in vitro treatment of mesenchymal stromal cells with GDF-5 and R57A induces chondrogenic differentiation while limiting chondrogenic hypertrophy
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-357770
- Purpose Hypertrophic cartilage is an important characteristic of osteoarthritis and can often be found in patients suffering from osteoarthritis. Although the exact pathomechanism remains poorly understood, hypertrophic de-differentiation of chondrocytes also poses a major challenge in the cell-based repair of hyaline cartilage using mesenchymal stromal cells (MSCs). While different members of the transforming growth factor beta (TGF-β) family have been shown to promote chondrogenesis in MSCs, the transition into a hypertrophic phenotypePurpose Hypertrophic cartilage is an important characteristic of osteoarthritis and can often be found in patients suffering from osteoarthritis. Although the exact pathomechanism remains poorly understood, hypertrophic de-differentiation of chondrocytes also poses a major challenge in the cell-based repair of hyaline cartilage using mesenchymal stromal cells (MSCs). While different members of the transforming growth factor beta (TGF-β) family have been shown to promote chondrogenesis in MSCs, the transition into a hypertrophic phenotype remains a problem. To further examine this topic we compared the effects of the transcription growth and differentiation factor 5 (GDF-5) and the mutant R57A on in vitro chondrogenesis in MSCs. Methods Bone marrow-derived MSCs (BMSCs) were placed in pellet culture and in-cubated in chondrogenic differentiation medium containing R57A, GDF-5 and TGF-ß1 for 21 days. Chondrogenesis was examined histologically, immunohistochemically, through biochemical assays and by RT-qPCR regarding the expression of chondrogenic marker genes. Results Treatment of BMSCs with R57A led to a dose dependent induction of chondrogenesis in BMSCs. Biochemical assays also showed an elevated glycosaminoglycan (GAG) content and expression of chondrogenic marker genes in corresponding pellets. While treatment with R57A led to superior chondrogenic differentiation compared to treatment with the GDF-5 wild type and similar levels compared to incubation with TGF-ß1, levels of chondrogenic hypertrophy were lower after induction with R57A and the GDF-5 wild type. Conclusions R57A is a stronger inducer of chondrogenesis in BMSCs than the GDF-5 wild type while leading to lower levels of chondrogenic hypertrophy in comparison with TGF-ß1.…
Autor(en): | Manuel Weißenberger, Mike Wagenbrenner, Joachim Nickel, Rasmus Ahlbrecht, Torsten Blunk, Andre F. Steinert, Fabian Gilbert |
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URN: | urn:nbn:de:bvb:20-opus-357770 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Lehrstuhl für Orthopädie |
Medizinische Fakultät / Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie (Chirurgische Klinik II) | |
Medizinische Fakultät / Lehrstuhl für Tissue Engineering und Regenerative Medizin | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Journal of Experimental Orthopaedics |
Erscheinungsjahr: | 2023 |
Band / Jahrgang: | 10 |
Aufsatznummer: | 29 |
Originalveröffentlichung / Quelle: | Journal of Experimental Orthopaedics (2023) 10:29. https://doi.org/10.1186/s40634-023-00594-z |
DOI: | https://doi.org/10.1186/s40634-023-00594-z |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | GDF-5; R57A; bone marrow; cartilage; chondrogenesis; chondrogenic hypertrophy; mesenchymal stromal cell |
Datum der Freischaltung: | 28.05.2024 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |