Document Detail

Hypertrophy in mesenchymal stem cell chondrogenesis: effect of TGF-beta isoforms and chondrogenic conditioning.
MedLine Citation:
PMID:  20407224     Owner:  NLM     Status:  MEDLINE    
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-beta3, which has been shown to be more prochondrogenic compared to TGF-beta1, 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-beta1 or TGF-beta3. 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-beta1 and TGF-beta3. 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.
Michael B Mueller; Maria Fischer; Johannes Zellner; Arne Berner; Thomas Dienstknecht; Lukas Prantl; Richard Kujat; Michael Nerlich; Rocky S Tuan; Peter Angele
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2010-04-20
Journal Detail:
Title:  Cells, tissues, organs     Volume:  192     ISSN:  1422-6421     ISO Abbreviation:  Cells Tissues Organs (Print)     Publication Date:  2010  
Date Detail:
Created Date:  2010-08-17     Completed Date:  2011-04-11     Revised Date:  2011-08-03    
Medline Journal Info:
Nlm Unique ID:  100883360     Medline TA:  Cells Tissues Organs     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  158-66     Citation Subset:  IM    
Copyright Information:
Copyright 2010 S. Karger AG, Basel.
Department for Trauma Surgery, Regensburg University Medical Center, Regensburg, Germany.
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MeSH Terms
Alkaline Phosphatase / metabolism
Calcification, Physiologic / drug effects
Cell Differentiation / drug effects,  physiology*
Cell Enlargement / drug effects*
Chondrocytes / cytology*,  metabolism
Chondrogenesis / drug effects,  physiology*
Collagen Type I / metabolism
Collagen Type II / metabolism
Collagen Type X / metabolism
Culture Media, Conditioned / metabolism
DNA / metabolism
Extracellular Matrix / metabolism
Glycerophosphates / pharmacology
Glycosaminoglycans / metabolism
Mesenchymal Stem Cells / cytology*,  drug effects,  metabolism
Protein Isoforms / pharmacology
Transforming Growth Factor beta / pharmacology*
Transforming Growth Factor beta1 / pharmacology
Transforming Growth Factor beta3 / pharmacology
Young Adult
Grant Support
Reg. No./Substance:
0/Collagen Type I; 0/Collagen Type II; 0/Collagen Type X; 0/Culture Media, Conditioned; 0/Glycerophosphates; 0/Glycosaminoglycans; 0/Protein Isoforms; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 0/Transforming Growth Factor beta3; 17181-54-3/beta-glycerophosphoric acid; 64082-61-7/A73025; 9007-49-2/DNA; EC Phosphatase

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