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Mediation of osteogenic differentiation of human mesenchymal stem cells on titanium surfaces by a Wnt-integrin feedback loop.
- Source :
-
Biomaterials [Biomaterials] 2011 Sep; Vol. 32 (27), pp. 6399-411. Date of Electronic Publication: 2011 Jun 01. - Publication Year :
- 2011
-
Abstract
- Peri-implant bone formation depends on the ability of mesenchymal cells to colonize the implant surface and differentiate into osteoblasts. Human mesenchymal stem cells (HMSCs) undergo osteoblastic differentiation on microstructured titanium (Ti) surfaces in the absence of exogenous factors, but the mechanisms are unknown. Wnt proteins are associated with an osteoblast phenotype, but how Wnt signaling regulates HMSC differentiation on microstructured Ti surfaces is not known. HMSCs were cultured on tissue culture polystyrene or Ti (PT [Sa = 0.33 μm, θ = 96°], SLA [Sa = 2.5 μm, θ = 132°], modSLA [hydrophilic-SLA]). Expression of calcium-dependent Wnt ligand WNT5A increased and canonical Wnt pathway ligands decreased on microstructured Ti in a time-dependent manner. Treatment of HMSCs with canonical ligand Wnt3a preserved the mesenchymal phenotype on smooth surfaces. Treatment with Wnt5a increased osteoblastic differentiation. Expression of integrins ITGA1, ITGA2, and ITGAV increased over time and correlated with increased WNT5A expression. Treatment of HMSCs with Wnt5a, but not Wnt3a, increased integrin expression. Regulation of integrin expression due to surface roughness and energy was ablated in WNT5A-knockdown HMSCs. This indicates that surface properties regulate stem cell fate and induce osteoblast differentiation via the Wnt calcium-dependent pathway. Wnt5a enhances osteogenesis through a positive feedback with integrins and local factor regulation, particularly though BMP signaling.<br /> (Copyright © 2011. Published by Elsevier Ltd.)
- Subjects :
- Gene Expression Regulation drug effects
Humans
Hydrophobic and Hydrophilic Interactions drug effects
Integrins genetics
Mesenchymal Stem Cells drug effects
Mesenchymal Stem Cells metabolism
Signal Transduction drug effects
Signal Transduction genetics
Surface Properties drug effects
Thermodynamics
Time Factors
Wnt Proteins genetics
Cell Differentiation drug effects
Feedback, Physiological drug effects
Integrins metabolism
Mesenchymal Stem Cells cytology
Osteogenesis drug effects
Titanium pharmacology
Wnt Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5905
- Volume :
- 32
- Issue :
- 27
- Database :
- MEDLINE
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 21636130
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2011.05.036