Original ArticleSynergistic effect of nanomaterials and BMP-2 signalling in inducing osteogenic differentiation of adipose tissue-derived mesenchymal stem cells
Graphical abstract
Illustration of how bone structure biomimetic nBG-PCL/HA/TCP scaffolds synergize BMP-2 signalling to promote osteogenic differentiation in ASCs through a mechanism of activation β1 integrin and Wnt-3a autocrine signalings.
Section snippets
Culturing of ASCs
ASCs (purchased from Invitrogen) were propagated until passage 4 according to the manufacturer's instructions in MesenPRO RSTM Basal Medium (Invitrogen) supplemented with 2 mM l-glutamine and MesenPRO RS Growth Supplement (Invitrogen). ASCs at passage 4 were used for all experiments.
Fabrication of HA/TCP and nBG-PCL/HA/TCP scaffolds
The method of fabricating HA/TCP and nBG-PCL/HA/TCP scaffolds have been previously described in detail.15 Briefly, calcium phosphate deficient apatite powder was prepared by an aqueous precipitation reaction and
3 days of BMP-2 pre-conditioning induced osteogenic differentiation of ASCs
Compared to ASCs without BMP-2 pre-conditioning, ASCs treated with BMP-2 (50 ng/ml) for 3 days showed significantly higher levels of Runx-2, collagen type I, osteopontin, and bone sialoprotein gene expression (Figure 1, A-D) and ALP enzyme activity (Figure 1, E) at 4 and 14 days, compared to ASCs without BMP-2.
nBG-PCL/HA/TCP scaffold surface supported the attachment and growth of ASCs
The surface of nBG-PCL/HA/TCP scaffolds were characterised by SEM analysis. Spherical-shaped nBG with average size of 20-50 nm in diameter were well dispersed on the nBG-PCL/HA/TCP scaffold
Discussion
This study was aimed to gain insight into the interactions between BMP-2 and nBG-PCL/HA/TCP scaffold in directing osteogenic differentiation of ASCs and the underlying signalling pathways that dictates ASCs fate, so that we are able to create such conditions for bone tissue regeneration. We demonstrated that the BMP-2 and nBG-PCL/HA/TCP scaffolds had a synergistic effect in inducing osteogenic differentiation in ASCs by involving a mechanism of activating β1-integrin and induction of Wnt-3a
References (45)
- et al.
The potential of human fetal mesenchymal stem cells for off-the-shelf bone tissue engineering application
Biomaterials
(2012) - et al.
Bone structure and formation: a new perspective
Mater Sci Eng Rep
(2007) BMP2 signaling in bone development and repair
Cytokine Growth Factor Rev
(2009)- et al.
Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells
Gene
(2006) - et al.
Temporal pattern of gene expression and histology of stress fracture healing
Bone
(2010) - et al.
Stem cell-biomaterial interactions for regenerative medicine
Biotechnol Adv
(2012) - et al.
Unique microstructural design of ceramic scaffolds for bone regeneration under load
Acta Biomater
(2013) - et al.
Effects of bioactive glass nanoparticles on the mechanical and biological behavior of composite coated scaffolds
Acta Biomater
(2011) - et al.
Bone nodules on chitosan-polygalacturonic acid-hydroxyapatite nanocomposite films mimic hierarchy of natural bone
Acta Biomater
(2011) - et al.
Bone biomimetic microenvironment induces osteogenic differentiation of adipose tissue-derived mesenchymal stem cells
Nanomedicine
(2012)
The influence hydroxyapatite nanoparticle shape and size on the properties of biphasic calcium phosphate scaffolds coated with hydroxyapatite-PCL composites
Biomaterials
A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned
Spine J
Wnt signaling pathway in rheumatoid arthritis, with special emphasis on the different roles in synovial inflammation and bone remodeling
Cell Signal
Hydroxyapatite coating affects the Wnt signaling pathway during peri-implant healing in vivo
Acta Biomater
Lithium chloride attenuates BMP-2 signaling and inhibits osteogenic differentiation through a novel WNT/GSK3-independent mechanism
Bone
Impaired bone formation in transgenic mice resulting from altered integrin function in osteoblasts
Dev Biol
The promotion of bone regeneration by nanofibrous hydroxyapatite/chitosan scaffolds by effects on integrin-BMP/Smad signaling pathway in BMSCs
Biomaterials
beta-Tricalcium phosphate exerts osteoconductivity through alpha2beta1 integrin and down-stream MAPK/ERK signaling pathway
Biochem Biophys Res Commun
A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics
Biomaterials
Modification of porous calcium phosphate surfaces with different geometries of bioactive glass nanoparticles
Mater Sci Eng C
Concepts of fracture union, delayed union, and nonunion
Clin Orthop Relat Res
Autogenous iliac crest bone graft. Complications and functional assessment
Clin Orthop Relat Res
Cited by (0)
The authors acknowledge the Australian National Health and Medical Research Council (NHMRC) and the Faculty of Engineering and IT at University of Sydney, for funding this project. The authors also acknowledge the Rebecca Cooper Foundation, and the facilities provided by School of AMME and the Bosch Institute at the University of Sydney.
Conflicts of interest: There are no interest conflicts to declare.