Opposite Spectrum of Activity of Canonical Wnt Signaling in the Osteogenic Context of Undifferentiated and Differentiated Mesenchymal Cells: Implications for Tissue Engineering

Quarto, Natalina; Behr, Björn; Longaker, Michael T.

doi:10.1089/ten.tea.2010.0133

Cited by 46 publications

(40 citation statements)

References 50 publications

(84 reference statements)

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“…Although most of previous studies have reported its inhibitory effect [22,33], there are a few reports describing its stimulatory effect [17,20], as also observed in the present study. The conflicting results could possibly be due to differences in the state of differentiation of the cells used, species of the cells, methods used to activate Wnt3a signaling and Wnt3a concentration, as previously reported [34]. It is thus important to further examine the detailed mechanism of the Wnt3a signaling pathway.…”

Section: Discussionmentioning

confidence: 96%

Osteogenic potency of stem cell-based genetic engineering targeting Wnt3a and Wnt9a

Singhatanadgit

Varodomrujiranon

2011

Open Life Sciences

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Bone engineering is a promising therapeutic approach to correct skeletal defects, and genetically-modified stem cells have been implicated in engineering new bone. However, the use of genetically-modified human mesenchymal stem cells targeting an osteogenic growth factor Wnt is not yet investigated. In the present study, a proliferation assay and the alkaline phosphatase (ALP) activity and expression of runt-related transcription factor 2 (Runx2) and osteocalcin (OC) transcripts were investigated to examine the effect of Wnt2 overexpression, Wnt3a overexpression, and Wnt9a knockdown on cell proliferation and osteoblast differentiation of bone marrowderived mesenchymal stem cells (BMSCs). The results showed that the expression of Wnt2 and Wnt3a was up-regulated throughout the osteoblast differentiation period of BMSCs, whereas that of Wnt9a was down-regulated. Overexpression of Wnt3a stimulated cell proliferation while knockdown of Wnt9a increased the ALP activity and the expression of Runx2 and OC. Double transfection producing Wnt3a overexpression and Wnt9a knockdown simultaneously resulted in up-regulation of osteoblast differentiation markers, i.e., the ALP activity and the Runx2 expression. In conclusion, simultaneous genetic modification of Wnt3a overexpression and Wnt9a knockdown enhances osteoblast differentiation of BMSCs, suggesting its osteogenic potency to regenerate new bone in vivo.

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Section: Discussionmentioning

confidence: 96%

Osteogenic potency of stem cell-based genetic engineering targeting Wnt3a and Wnt9a

Singhatanadgit

Varodomrujiranon

2011

Open Life Sciences

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“…(Quarto, Longaker 2010). Low dose treatment with Wnt3a enhanced bony regeneration in a mouse critical calvarial defect treated with differing doses of Wnt3a in juvenile mice, while higher doses decreased repair (Quarto, Longaker 2010). Conversely, in adult mice, increasing doses of Wnt3a enhanced bone regeneration.…”

Section: Molecular Pathways Of Differentiationmentioning

confidence: 99%

“…Wnt3A has been shown to have differing results on osteogenic differentiation depending on dosage and level of baseline differentiation along with age of the cells. (Quarto, Longaker 2010). Low dose treatment with Wnt3a enhanced bony regeneration in a mouse critical calvarial defect treated with differing doses of Wnt3a in juvenile mice, while higher doses decreased repair (Quarto, Longaker 2010).…”

Section: Molecular Pathways Of Differentiationmentioning

confidence: 99%

Tissue Engineering for Tissue and Organ Regeneration

Eberli¹

2011

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“…Moreover, a series of studies have demonstrated the importance of the canonical Wnt pathway in promoting osteogenesis in vivo and in vitro (Chung et al, 2009). Quarto et al (Quarto et al, 2010) evidenced that canonical Wnt signaling pathway can inhibit or promote osteogenesis, depending on the cell differentiation stage or on Wnt ligand concentration. During the osteogenic differentiation this signaling pathway interferes with RUNX2 and OSX (Hill et al, 2005).…”

Section: A Wnt Signaling Pathwaymentioning

confidence: 99%

An overview on osteogenic differentiation process: Minimum essential information for bone tissue engineering

Șelaru¹,

Samoilă²,

Dinescu³

et al. 2018

Rev. Biol. Biomed. Sci.

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Bone tissue engineering is a new and modern strategy that serves for repairing major bone defects. Three essential elements are involved in bone tissue engineering: a scaffold, a cell source that can convert into bone cells and growth factors. In order to develop new and original biomaterials with high compatibility it is necessary to fully understand osteoblastogenesis. Osteoblasts and osteoclasts are the two types of cells involved in the formation of bone tissue. Osteoblasts are cells responsible for bone growth and for synthesizing bone matrix, whereas osteoclasts function in bone resorbtion. There are some osteogenic markers that osteoblasts are able to produce during bone formation, that have an important role in the processes of migration, proliferation and differentiation. Also, the differentiation process is governed by three major signaling pathways: Wnt, Hedgehog and Notch, which have the role to regulate osteogenesis by controlling proliferation, differentiation and apoptosis. This review aims to synthesize the most important information known so far regarding the main stages and markers of osteogenesis, as well as the main biomaterials, major cell types and specific osteogenic inducers involved in bone tissue engineering. Moreover, this review can serve as a guideline for further applications concerning this subject.

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Opposite Spectrum of Activity of Canonical Wnt Signaling in the Osteogenic Context of Undifferentiated and Differentiated Mesenchymal Cells: Implications for Tissue Engineering

Cited by 46 publications

References 50 publications

Osteogenic potency of stem cell-based genetic engineering targeting Wnt3a and Wnt9a

Osteogenic potency of stem cell-based genetic engineering targeting Wnt3a and Wnt9a

Tissue Engineering for Tissue and Organ Regeneration

An overview on osteogenic differentiation process: Minimum essential information for bone tissue engineering

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