Wnt signaling and skeletal development

Liu, Fei; Kohlmeier, Sean; Wang, Cun Yu

doi:10.1016/j.cellsig.2007.11.011

Cited by 134 publications

(110 citation statements)

References 108 publications

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…In vitro, the cellular effects of Wnt3a has been reported to be cell type-and culture conditiondependent. (42) In vivo, Wnt3a has been shown to accelerate the healing process of bone repair when delivered in liposomes at injury sites. (41) This effect of Wnt3a was mainly the result of enhanced proliferation of skeletal progenitors and acceleration of their differentiation into osteoblasts.…”

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 99%

Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation

Caverzasio

Thouverey

2012

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Previous studies have shown that Wnt3a enhances the proliferation and inhibits the osteogenic differentiation of human mesenchymal stem cells (hMSCs). In this study, we investigated the signaling pathways involved in Wnt3a-induced osteoblastic cell proliferation. Experiments with DKK1, a natural antagonist of Lrp5/6, indicated that Wnt/b-catenin did not play a major role in Wnt3a-induced osteoblastic cell proliferation. The use of selective inhibitors of known mitogenic pathways implicates Src family kinases (SFKs) and a protein kinase C (PKC) in this cellular response. Time-dependent analysis of signaling molecules activated by Wnt3a in MC3T3-E1 cells revealed parallel activation of the canonical pathway and of several tyrosine kinases, including SFKs and PDGF receptors (PDGF-Rs). Functional analysis with specific inhibitors suggested a major role of PDGF-Rs in mediating Wnt3a-induced cell proliferation. Further investigation with an si-RNA approach confirmed a predominant role of this receptor in this cellular response. The use of soluble decoy PDGF-Rs that can sequester extracellular PDGFs excluding that part of the increased PDGF receptor phosphorylation by Wnt3a was the result of autocrine production of PDGFs. A selective SFK inhibitor blunted the enhanced PDGF-R phosphorylation and cell proliferation induced by Wnt3a. Studies of initial events involved in the regulation of this pathway suggest a role of dishevelled. In conclusion, data presented in this study indicate that cell proliferation induced by Wnt3a in osteoblastic cells is mediated by a dishevelleddependent and b-catenin-independent pathway, which involves the transactivation of PDGF receptors. ß

show abstract

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 99%

Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation

Caverzasio

Thouverey

2012

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…In addition, 7% (1.54 Â 10 À30 < p < 4.41 Â 10 À4 ) of the transcripts are clustered to skeletal development, including known genes such as IL8 (129-fold), CCND1 (14-fold), CSF2 (13-fold), CD44 (11.8-fold), RAC2 (10.4-fold), FOSL1 (9.5-fold), and Sox9 (5-fold). Further analysis of signaling pathways revealed the upregulation of pathways that play essential roles during bone formation and mesenchymal differentiation, such as Wnt/b-catenin signaling, (57) ERK/MAPK signaling, (58) epidermal growth factor (EGF) signaling, (59) and vascular endothelial growth factor (VEGF) signaling (60) (Supplemental Table 4). …”

Section: Differentiation Of Sb-og Cells Into Mesenchymal Progenitorsmentioning

confidence: 99%

Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-β/activin/nodal signaling using SB-431542

Mahmood

Harkness²,

Schrøder

et al. 2010

Journal of Bone and Mineral Research

112

View full text Add to dashboard Cite

Directing differentiation of human embryonic stem cells (hESCs) into specific cell types using an easy and reproducible protocol is a prerequisite for the clinical use of hESCs in regenerative-medicine procedures. Here, we report a protocol for directing the differentiation of hESCs into mesenchymal progenitor cells. We demonstrate that inhibition of transforming growth factor b (TGF-b)/activin/nodal signaling during embryoid body (EB) formation using SB-431542 (SB) in serum-free medium markedly upregulated paraxial mesodermal markers (TBX6, TBX5) and several myogenic developmental markers, including early myogenic transcriptional factors (Myf5, Pax7), as well as myocyte-committed markers [NCAM, CD34, desmin, MHC (fast), a-smooth muscle actin, Nkx2.5, cTNT]. Continuous inhibition of TGF-b signaling in EB outgrowth cultures (SB-OG) enriched for myocyte progenitor cells; markers were PAX7 þ (25%), MYOD1 þ (52%), and NCAM þ (CD56) (73%). DNA microarray analysis revealed differential upregulation of 117 genes (>2-fold compared with control cells) annotated to myogenic development and function. Moreover, these cells showed the ability to contract (80% of the population) and formed myofibers when implanted intramuscularly in vivo. Interestingly, SB-OG cells cultured in 10% fetal bovine serum (FBS) developed into a homogeneous population of mesenchymal progenitors that expressed CD markers characteristic of mesenchymal stem cells (MSCs): CD44 þ (100%), CD73 þ (98%), CD146 þ (96%), and CD166 þ (88%) with the ability to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and in vivo. Furthermore, microarray analysis of these cells revealed downregulation of genes related to myogenesis: MYH3 (À167.9-fold), ACTA1 (À161-fold), MYBPH (À139-fold), ACTC (À100.3-fold), MYH8 (À45.5-fold), and MYOT (À41.8-fold) and marked upregulation of genes related to mesoderm-derived cell lineages. In conclusion, our data provides a simple and versatile protocol for directing the differentiation of hESCs into a myogenic lineage and then further into mesenchymal progenitors by blocking the TGF-b signaling pathway. ß

show abstract

“…Previous studies have shown that FGF (Ornitz and Marie, 2002), BMP (Chen et al, 2004) and WNT pathways (Liu et al, 2008) are important signaling networks coexisting within bone cells during development and carcinogenesis. The FGF-PI3K-AKT signaling pathway and the canonical WNT signaling pathway cross talk at glycogen synthase kinase-b during carcinogenesis (Katoh, 2006), whereas FGF and BMP share MAPKdependent pathways in regulating osteogenesis (Franceschi and Xiao, 2003).…”

Section: Ra-mediated Rara Hypophosphorylation Induces Fgf8f Expressionmentioning

confidence: 99%

Retinoid-suppressed phosphorylation of RARα mediates the differentiation pathway of osteosarcoma cells

et al. 2010

View full text Add to dashboard Cite

Wnt signaling and skeletal development

Cited by 134 publications

References 108 publications

Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation

Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation

Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-β/activin/nodal signaling using SB-431542

Retinoid-suppressed phosphorylation of RARα mediates the differentiation pathway of osteosarcoma cells

Contact Info

Product

Resources

About