Hypertrophy in Mesenchymal Stem Cell Chondrogenesis: Effect of TGF-beta Isoforms and Chondrogenic Conditioning

Mueller, Michael B. and Fischer, Maria and Zellner, Johannes and Berner, Arne and Dienstknecht, Thomas and Prantl, Lukas and Kujat, Richard and Nerlich, Michael and Tuan, Rocky S. and Angele, Peter (2010) Hypertrophy in Mesenchymal Stem Cell Chondrogenesis: Effect of TGF-beta Isoforms and Chondrogenic Conditioning. CELLS TISSUES ORGANS, 192 (3). pp. 158-166. ISSN 1422-6405,

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Abstract

Induction of chondrogenesis in mesenchymal stem cells (MSCs) with TGF-beta leads to a hypertrophic phenotype. The hypertrophic maturation of the chondrocytes is dependent on the timed removal of TGF-beta and sensitive to hypertrophy-promoting agents in vitro. In this study, we have investigated whether TGF-beta 3, which has been shown to be more pro-chondrogenic compared to TGF-beta 1, similarly enhances terminal differentiation in an in vitro hypertrophy model of chondrogenically differentiating MSCs. In addition, we tested the impact of the time of chondrogenic conditioning on the enhancement of hypertrophy. MSCs were chondrogenically differentiated in pellet culture in medium containing TGF-beta 1 or TGF-beta 3. After 2 or 4 weeks, chondrogenic medium was switched to hypertrophy-inducing medium for 2 weeks. Aggregates were analyzed histologically and biochemically on days 14, 28 and 42. The switch to hypertrophy medium after 14 days induced hypertrophic cell morphology and significant increase in alkaline phosphatase activity compared to the chondrogenesis only control using both TGF-beta 1 and TGF-beta 3. After 28 days predifferentiation, differences between hypertrophic and control groups diminished compared to 14 days predifferentiation. In conclusion, chondrogenic conditioning with both TGF-beta isoforms similarly induced hypertrophy in our experiment and allowed the enhancement of the hypertrophic chondrocyte phenotype by hypertrophic medium. Enhancement of hypertrophy was seen more clearly after the shorter chondrogenic conditioning. Therefore, to utilize this experimental model as a tool to study hypertrophy in MSC chondrogenesis, a predifferentiation period of 14 days is recommended. Copyright (C) 2010 S. Karger AG, Basel

Item Type: Article
Uncontrolled Keywords: VITRO CARTILAGE FORMATION; BONE-MARROW; PROGENITOR CELLS; ENDOCHONDRAL OSSIFICATION; CHONDROCYTE MATURATION; MOLECULAR EVENTS; GENE-EXPRESSION; DIFFERENTIATION; CULTURE; GROWTH; Bone marrow stromal cell; Cartilage biology; Cartilage repair; Cell biology; Chondrogenic differentiation; Hypertrophy; Mesenchymal progenitor cell differentiation; Mesenchymal stem cells; Tissue engineering
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Unfallchirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 12 Aug 2020 08:57
Last Modified: 12 Aug 2020 08:57
URI: https://pred.uni-regensburg.de/id/eprint/25379

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