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Activin and Nodal Are Not Suitable Alternatives to TGF beta for Chondrogenic Differentiation of Mesenchymal Stem Cells
- Source :
- Cartilage, 8, 432-438, Cartilage, 8(4), 432-438. SAGE Publishing, Cartilage, 8, 4, pp. 432-438
- Publication Year :
- 2017
-
Abstract
- Objective Previously, we demonstrated the importance of transforming growth factor-β (TGFβ)-activated SMAD2/3 signaling in chondrogenesis of bone marrow–derived mesenchymal stem cells (BMSCs). However, TGFβ also signals via the SMAD1/5/9 pathway, which is known to induce terminal differentiation of BMSCs. In this study, we investigated whether other SMAD2/3-activating ligands, Activin and Nodal, can induce chondrogenic differentiation of BMSCs without inducing terminal differentiation. Design Activation of SMAD2/3 signaling and chondrogenesis were evaluated in human BMSCs ( N = 3 donors) stimulated with TGFβ, Activin, or Nodal. SMAD2/3 activation was assessed by determining phosphorylated-SMAD2 (pSMAD2) protein levels and SMAD2/3-target gene expression of SERPINE1. Chondrogenesis was determined by ACAN and COL2A1 transcript analysis and histological examination of proteoglycans and collagen type II. Results Both Activin and TGFβ enhanced pSMAD2 and SERPINE1 expression compared to the control condition without growth factors, demonstrating activated SMAD2/3 signaling. pSMAD2 and SERPINE1 had a higher level of expression following stimulation with TGFβ than with Activin, while Nodal did not activate SMAD2/3 signaling. Of the 3 ligands tested, only TGFβ induced chondrogenic differentiation as shown by strongly increased transcript levels of ACAN and COL2A1 and positive histological staining of proteoglycans and collagen type II. Conclusions Even with concentrations up to 25 times higher than that of TGFβ, Activin and Nodal do not induce chondrogenic differentiation of BMSCs; thus, neither of the 2 ligands is an interesting alternative candidate for TGFβ to induce chondrogenesis without terminal differentiation. To obtain stable cartilage formation by BMSCs, future studies should decipher how TGFβ-induced terminal differentiation can be prevented.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Chemistry
Mesenchymal stem cell
Biomedical Engineering
Physical Therapy, Sports Therapy and Rehabilitation
Stimulation
Chondrogenesis
Cell biology
Basic in vitro Studies
03 medical and health sciences
All institutes and research themes of the Radboud University Medical Center
030104 developmental biology
Endocrinology
stomatognathic system
Internal medicine
Gene expression
TGF beta signaling pathway
medicine
Immunology and Allergy
NODAL
Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Activin type 2 receptors
Transforming growth factor
Subjects
Details
- ISSN :
- 19476035
- Database :
- OpenAIRE
- Journal :
- Cartilage, 8, 432-438, Cartilage, 8(4), 432-438. SAGE Publishing, Cartilage, 8, 4, pp. 432-438
- Accession number :
- edsair.doi.dedup.....986d9983e5a978954718801b25b85d67