Modulating osteogenesis of mesenchymal stem cells by modifying growth factor availability

Huang, Zhu; Ren, Pei‐Gen; Ma, Ting; Smith, Robert L.; Goodman, Stuart B.

doi:10.1016/j.cyto.2010.06.002

Cited by 121 publications

(90 citation statements)

References 41 publications

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“…The regulation of growth factors and hormones, such as transform growth factor beta (TGF-β), fibroblast growth factor (FGF), insulin-like growth factor 1 (IGF-1), bone morphogenetic protein (BMP) and parathormone (PTH), on MSCs proliferation and differentiation have been studied thoroughly (Haddad and Harb 2005;Qi et al 2009;Huang et al 2010). It has been reported that MSCs cultured in vitro would differentiate into osteoblasts spontaneously (Seong et al 2010;Mikami et al 2011).…”

mentioning

confidence: 99%

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Huang

Deng

Wang

et al. 2011

Tohoku J. Exp. Med.

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Mesenchymal stem sells (MSCs) have received much attention in the field of bone tissue engineering due to their biological capability to differentiate into osteogenic lineage cells. Hypoxia-inducible factor 1alpha (HIF-1α) plays an important role in the MSC-related bone regeneration during hypoxia, while core binding factor alpha 1 (Cbfα1) is a transcription regulator that is involved in the chondrocyte differentiation and ossification. In the present study, we investigated the effects of hypoxia on biological capability of MSCs. MSCs were isolated from adult rabbit bone marrow, and were cultured in vitro under normoxia (air with 5% CO 2 ) or hypoxia (5% CO 2 and 95% N 2 ). The proliferation of MSCs, alkaline phosphatase (ALP) activity, and production of collagens type I and type III (Col I/III) were examined. The expression levels of HIF-1α and Cbfα1 were measured by real-time PCR and western blot analyses. We found that hypoxia significantly induced the proliferation of MSCs and increased ALP activity and the production of Col I/III. Moreover, hypoxia increased the expression of Cbfα1 mRNA after 12 h, whereas the expression of HIF-1α mRNA was increased after 1 h of hypoxia. Knockdown of HIF-1α expression with a small interfering RNA significantly increased the expression levels of Cbfα1 protein either under the normoxia or hypoxia condition. Our results indicate that hypoxia enhances MSCs to differentiate into osteogenic lineage cells and suggest that Cbfα1 may be negatively regulated by HIF-1α.

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confidence: 99%

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Huang

Deng

Wang

et al. 2011

Tohoku J. Exp. Med.

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“…Overall the addiction of GF (rhBMP-2) has greatly increased osteocalcin level (OC) released from MSC. This study stated that endogenous IGF-l and FGF-2 are essential to osteogenesis, but also that excess IGF-l and FGF-2 are inhibitory to bone formation (18) .…”

Section: Resultsmentioning

confidence: 99%

“…(9,12,15,16,17,18,19,20,21). In a recent study about chondrogenic and osteogenic differentiation ofMSC (20) it was demonstrated rhBMP-7 enhances the upregulation of lineage-specific markers, such as type II and type IX collagens (COL2Al, COL9Al) in chondrogenic, and secretes phosphoprotein 1 (SPPl), osteocalcin (BGLAP) and osterix (SP7) in osteogenic differentiation; this is due to the property of increasing alkaline phosphatase activity and to the dose-dependent capacity to accelerate mineralization of osteogenic differentiated MSC.…”

Section: Resultsmentioning

confidence: 99%

Polytherapy in Bone Regeneration: Clinical Applications and Preliminary Considerations

Calori

Colombo

Ripamonti

et al. 2011

Int J Immunopathol Pharmacol

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Polytherapy, namely the simultaneous application of three fundamental elements necessary for bone regeneration (growth factors, osteogenic cells and osteocnductive scaffolds) seems to lead to a very high success rate in the treatment of complex non-union (NU) cases and critical bone defects. NU are reported in 5–10% of long bone fractures. The use of autologous bone grafts has been long-considered the gold standard for the treatment of these cases. However the harvesting procedure from the iliac crest increases surgery time and presents some donor site complications which may be elevated. In recent years, surgeons have some alternatives to autologous grafting such as: application of organic or synthetic bone substitute, application of mesenchymal stromal cells (MSC) or growth factors (GF). In the literature there are many studies available about their application in monotherapy, but unfortunately the healing rate doesn't exceed 90%. Polytherapy seems to be a logical option to improve the healing rate, nevertheless, there are not still extensive studies that validate this strategy and moreover, some questions are not resolved.

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“…From this point of view, insulin-like growth factor (IGF)-1 and vascular endothelial growth factor (VEGF) are particularly engaging, since they have a key role in both bone and endothelial development [Allori et al, 2008;Huang et al, 2010].…”

Section: Introductionmentioning

confidence: 99%

Evidence Supporting a Paracrine Effect of IGF-1/VEGF on Human Mesenchymal Stromal Cell Commitment

Dicarlo

Bianchi²,

Ferretti³

et al. 2016

Cells Tissues Organs

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Healing of skeletal defects is strictly dependent on osteogenesis and efficient vascularization of engineered scaffolds. Insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) are both involved in these processes. The in vitro administration of IGF-1 in association with VEGF is able to modulate the osteoblastic or endothelial commitment of mesenchymal stromal cells (MSCs) of different origins (e.g. periosteum and skin). In the present study, in order to deepen a possible paracrine effect of IGF-1 and VEGF on periosteum-derived progenitor cells (PDPCs) and skin-derived MSCs (S-MSCs), a Transwell coculture approach was used. We explored the genes involved in endothelial and osteoblastic differentiation, those modulating mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3′-kinase (PI3K)-AKT signaling pathways as well as genes implicated in stemness (i.e. Sox2, Oct4, and Nanog). Periosteal cells, which are typically committed toward osteoblastogenesis, are driven in the direction of endothelial gene expression when influenced by S-MSCs. The latter, once influenced by PDPCs, lose their endothelial commitment and increase the expression of osteoblast-associated genes. PI3K/AKT and MAPK signaling pathways seem to be markedly involved in this behavior. Our results evidence that paracrine signals between MSCs may differently modulate their commitment in a bone microenvironment, opening stimulating viewpoints for skeletal tissue engineering strategies coupling angiogenesis and osteogenesis processes.

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Modulating osteogenesis of mesenchymal stem cells by modifying growth factor availability

Cited by 121 publications

References 41 publications

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Polytherapy in Bone Regeneration: Clinical Applications and Preliminary Considerations

Evidence Supporting a Paracrine Effect of IGF-1/VEGF on Human Mesenchymal Stromal Cell Commitment

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