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Hypertrophy In Mesenchymal Stem Cell Chondrogenesis: Effect Of TGF-β Isoforms And Chondrogenic Conditioning

Michael B. Mueller, Maria Clara Bueno Fischer, Johannes Zellner, Arne Berner, Thomas Dienstknecht, Lukas Prantl, Richard Kujat, M. Nerlich, Rocky S. Tuan, Peter Angele
Published 2010 · Biology, Medicine
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Induction of chondrogenesis in mesenchymal stem cells (MSCs) with TGF-β leads to a hypertrophic phenotype. The hypertrophic maturation of the chondrocytes is dependent on the timed removal of TGF-β and sensitive to hypertrophy-promoting agents in vitro. In this study, we have investigated whether TGF-β3, which has been shown to be more prochondrogenic compared to TGF-β1, 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-β1 or TGF-β3. 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-β1 and TGF-β3. After 28 days predifferentiation, differences between hypertrophic and control groups diminished compared to 14 days predifferentiation. In conclusion, chondrogenic conditioning with both TGF-β 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.
This paper references
10.1002/art.23370
Functional characterization of hypertrophy in chondrogenesis of human mesenchymal stem cells.
Michael B. Mueller (2008)
Growth and differentiation of the developing limb bud from the perspective of chon - drogenesis
L. Song (2007)
10.1089/ten.1998.4.415
Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow.
Alastair Morgan Mackay (1998)
10.1210/endo.138.11.5522
Modulation of commitment, proliferation, and differentiation of chondrogenic cells in defined culture medium.
Rodolfo Quarto (1997)
10.1006/excr.2001.5278
Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components.
Frank Barry (2001)
10.1002/bdrc.10014
Physiology and pathophysiology of the growth plate.
Robert Tracy Ballock (2003)
10.1002/(SICI)1097-4644(19970901)66:3<394::AID-JCB11>3.0.CO;2-F
Rapid chondrocyte maturation by serum-free culture with BMP-2 and ascorbic acid.
Phoebe S. Leboy (1997)
10.1074/jbc.M305312200
Transforming Growth Factor-β-mediated Chondrogenesis of Human Mesenchymal Progenitor Cells Involves N-cadherin and Mitogen-activated Protein Kinase and Wnt Signaling Cross-talk*
Richard Tuli (2003)
10.1002/ar.1092240207
Cartilage macromolecules and the calcification of cartilage matrix.
A. Robin Poole (1989)
10.1002/jor.20200
Limitations of using aggrecan and type X collagen as markers of chondrogenesis in mesenchymal stem cell differentiation.
Fackson Mwale (2006)
10.1359/jbmr.2001.16.2.309
A novel cell culture model of chondrocyte differentiation during mammalian endochondral ossification.
Joyce Cheung (2001)
10.1002/jor.1100130606
Regulation of chondrocyte maturation by fibroblast growth factor-2 and parathyroid hormone.
Masahiro Iwamoto (1995)
10.2106/00004623-199812000-00004
The Chondrogenic Potential of Human Bone-Marrow-Derived Mesenchymal Progenitor Cells*
Jung U. Yoo (1998)
10.1002/art.22136
Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice.
Karoliina Pelttari (2006)
10.1016/S0945-053X(00)00125-6
Endochondral ossification of costal cartilage is arrested after chondrocytes have reached hypertrophic stage of late differentiation.
S H Bahrami (2001)
10.1111/j.1440-169X.2007.00945.x
Growth and differentiation of the developing limb bud from the perspective of chondrogenesis.
Hirohito Shimizu (2007)
10.1006/dbio.1993.1200
TGF-beta 1 prevents hypertrophy of epiphyseal chondrocytes: regulation of gene expression for cartilage matrix proteins and metalloproteases.
Robert Tracy Ballock (1993)
10.1006/excr.1997.3858
In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells.
Brian H. Johnstone (1998)
10.1016/j.biomaterials.2004.03.005
A three-dimensional nanofibrous scaffold for cartilage tissue engineering using human mesenchymal stem cells.
W-J Wan-Ju Li (2005)
10.1089/ten.2006.12.2639
Suppression of genes related to hypertrophy and osteogenesis in committed human mesenchymal stem cells cultured on novel nitrogen-rich plasma polymer coatings.
Fackson Mwale (2006)
10.1002/jcb.20652
The control of chondrogenesis.
Mary B Goldring (2006)
10.1073/pnas.052716199
In vitro cartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis
Ichiro Sekiya (2002)
10.1007/s004180050397
Hypertrophy of growth plate chondrocytes in vivo is accompanied by modulations in the activity state and surface area of their cytoplasmic organelles
Ernst Bruno Hunziker (1999)
Growth and differentiation of the developing limb bud from the perspective of chon - drogenesis
D. Baksh (2007)
10.1007/BF02634003
Differentiation and mineralization in chick chondrocytes maintained in a high cell density culture: A model for endochondral ossification
Colin Farquharson (2007)
10.1007/s00441-005-1140-6
Morphological examination during in vitro cartilage formation by human mesenchymal stem cells
Shizuko Ichinose (2005)
10.1016/j.biomaterials.2005.02.031
Cellular and molecular events during chondrogenesis of human mesenchymal stromal cells grown in a three-dimensional hyaluronan based scaffold.
Gina Lisignoli (2005)
10.1080/14653240410005276-1
Mesenchymal stem cell-based cartilage tissue engineering: cells, scaffold and biology.
Lin Nan Song (2004)
10.1016/S0006-291X(03)00912-4
Thyroxine downregulates Sox9 and promotes chondrocyte hypertrophy.
Yasunori Okubo (2003)
10.1089/107632702753503126
In vitro engineered cartilage constructs produced by press-coating biodegradable polymer with human mesenchymal stem cells.
Ulrich Noeth (2002)
10.1002/jor.20233
Effects of TGF-beta1 and triiodothyronine on cartilage maturation: in vitro analysis using long-term high-density micromass cultures of chick embryonic limb mesenchymal cells.
Maria Alice Mello (2006)
10.1097/00003086-199910001-00017
Autologous mesenchymal progenitor cells in articular cartilage repair.
Brian H. Johnstone (1999)



This paper is referenced by
10.1088/1748-605X/ab401f
Hydrogel to guide chondrogenesis versus osteogenesis of mesenchymal stem cells for fabrication of cartilaginous tissues.
Jingming Chen (2019)
10.2492/INFLAMMREGEN.35.078
High capacity of purified mesenchymal stem cells for cartilage regeneration
Eriko Grace Suto (2015)
10.1089/ten.TEA.2011.0172
A comparison of human smooth muscle and mesenchymal stem cells as potential cell sources for tissue-engineered vascular patches.
Corin Williams (2012)
10.1002/jbm.a.34194
An in vitro study of collagen hydrogel to induce the chondrogenic differentiation of mesenchymal stem cells.
Li Zhang (2012)
Capability of Cartilage Extract to In Vitro Differentiation of Rat Mesenchymal Stem Cells (MSCs) to Chondrocyte Lineage
Setareh Talakoob (2015)
10.1089/TEN.TEB.2013.0760
The Application of Multiple Biophysical Cues to Engineer Functional Neocartilage for Treatment of Osteoarthritis. Part II: Signal Transduction
A BradyMariea (2015)
10.1002/adhm.201400773
Cartilage tissue engineering: recent advances and perspectives from gene regulation/therapy.
Kuei-Chang Li (2015)
10.1016/j.omtn.2019.05.029
miR-892b Inhibits Hypertrophy by Targeting KLF10 in the Chondrogenesis of Mesenchymal Stem Cells
Jong Min Lee (2019)
The development of glycosaminoglycan-based materials to promote chondrogenic differentiation of mesenchymal stem cells
Jeremy J. Lim (2012)
10.1007/s12015-018-9816-y
Improved Protocol for Chondrogenic Differentiation of Bone Marrow Derived Mesenchymal Stem Cells -Effect of PTHrP and FGF-2 on TGFβ1/BMP2-Induced Chondrocytes Hypertrophy
Davood Nasrabadi (2018)
10.1007/s00264-014-2619-0
The role of growth factors in stem cell-directed chondrogenesis: a real hope for damaged cartilage regeneration
Ewelina Augustyniak (2014)
10.1089/scd.2011.0150
Conversion of human bone marrow-derived mesenchymal stem cells into tendon progenitor cells by ectopic expression of scleraxis.
Paolo Alberton (2012)
10.1016/j.bmcl.2016.08.069
Potential therapeutic application of small molecule with sulfonamide for chondrogenic differentiation and articular cartilage repair.
Eunhyun Choi (2016)
A dive into TGFβ signaling components during generation and degeneration of cartilage
L. de Kroon (2017)
10.1016/j.jconrel.2015.03.026
TGF-β3 encapsulated PLCL scaffold by a supercritical CO2-HFIP co-solvent system for cartilage tissue engineering.
Su Hee Kim (2015)
10.1002/jor.24224
Enhancement of the chondrogenic differentiation of mesenchymal stem cells and cartilage repair by ghrelin.
Litong Fan (2019)
10.22203/ECM.V031A06
Chondrogenesis of mesenchymal stem cells in a novel hyaluronate-collagen-tricalcium phosphate scaffolds for knee repair.
Fanqiong Meng (2016)
10.1007/s00418-010-0760-4
Hydrolyzed fish collagen induced chondrogenic differentiation of equine adipose tissue-derived stromal cells
Oksana Raabe (2010)
10.17795/ZJRMS-6663
EFFECTS OF LOW INTENSITY ULTRASOUND ON THE CHONDROGENIC DIFFERENTIATION OF ADULT STEM CELLS FROM ADIPOSE TISSUE
Hajar Shafaei (2016)
10.1002/term.1918
Recapitulating endochondral ossification: a promising route to in vivo bone regeneration.
Emmet M. Thompson (2015)
10.3390/ijms21031046
TGF–β3 Loaded Electrospun Polycaprolacton Fibre Scaffolds for Rotator Cuff Tear Repair: An in Vivo Study in Rats
Janin Reifenrath (2020)
10.1016/j.actbio.2017.09.008
Enzyme-crosslinked gene-activated matrix for the induction of mesenchymal stem cells in osteochondral tissue regeneration.
Yi-Hsuan Lee (2017)
10.1557/mrc.2017.91
Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces.
Alexander J Boys (2017)
10.1016/j.gendis.2014.12.003
Strategies to minimize hypertrophy in cartilage engineering and regeneration
Song Chen (2015)
10.1007/978-1-61779-815-3_14
Isolation, culture, and osteogenic/chondrogenic differentiation of bone marrow-derived mesenchymal stem cells.
Susanne Grässel (2012)
10.1080/15368378.2020.1737809
Combination of low intensity electromagnetic field with chondrogenic agent induces chondrogenesis in mesenchymal stem cells with minimal hypertrophic side effects.
Roya Hesari (2020)
10.2217/RME.15.31
Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.
Carrie Gaut (2015)
10.15171/bi.2020.05
Comparative impact of platelet rich plasma and transforming growth factor-β on chondrogenic differentiation of human adipose derived stem cells
Roya Hesari (2020)
10.1089/ten.TEA.2015.0250
Accelerated Chondrogenic Differentiation of Human Perivascular Stem Cells with NELL-1.
Chenshuang Li (2016)
10.1039/C7TB02172K
Chondroinductive factor-free chondrogenic differentiation of human mesenchymal stem cells in graphene oxide-incorporated hydrogels.
He Shen (2018)
10.1002/adma.201505088
Delivering Nucleic-Acid Based Nanomedicines on Biomaterial Scaffolds for Orthopedic Tissue Repair: Challenges, Progress and Future Perspectives.
Rosanne M Raftery (2016)
10.1007/978-1-61779-815-3
Somatic Stem Cells
Shree Ram Singh (2012)
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