Wnt3a signaling promotes proliferation, myogenic differentiation, and migration of rat bone marrow mesenchymal stem cells

Shang, Yan Chang; Wang, Shu Hui; Xiong, Fu; Zhao, Chengliang; Peng, Fenfen; Feng, Shan Wei; Li, Mei Shan; Li, Yong; Zhang, Cheng

doi:10.1111/j.1745-7254.2007.00671.x

Cited by 70 publications

(64 citation statements)

References 41 publications

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“…As shown in several reports, osteogenesis, myogenesis and chondrogenesis are all promoted, while adipogenesis is the only mesenchymal developmental process, which is inhibited by WNT molecules (Zhou et al 2004, 2007, Akimoto et al 2005, Kennell & MacDougald 2005, Kirton et al 2007, Shang et al 2007a,b, Schilling et al 2008. For example, canonical WNT3A signalling in mesenchymal stem cells resulted in the induction of several pro-myogenic factors such as PAX7, MYOD and myogenin.…”

Section: Wnt Molecules In the Determination Of Preadipocytesmentioning

confidence: 99%

Role of WNT pathway in the determination of human mesenchymal stem cells into preadipocytes

Laudes¹

2011

Journal of Molecular Endocrinology

107

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The development of obesity is characterised not only by increased storage of lipids in existing fat cells but also by the generation of new adipocytes from progenitor cells. This process, called adipogenesis, can be divided into two related steps. First, during determination, multipotent mesenchymal stem cells commit to preadipocytes. These cells exhibit similar morphology compared with stem cells; however, they are committed to the adipogenic lineage and are not longer able to transform into osteoblasts, myocytes or chondrocytes. Secondly, during differentiation, preadipocytes become mature fat cells. As in other developmental processes, adipogenesis is tightly regulated at a molecular level by several transcription factors. Within the last decade, it has also become clear how the activity of these transcription factors is coordinated by extracellular signals. In this respect, secreted WNT signalling molecules are particularly important. Several members of the WNT family have been shown to inhibit early steps of adipogenesis. Conversely, endogenous inhibitors of WNT signalling were found to promote generation of adipocytes, indicating a fundamental role of these bioactive peptides in adipogenesis. From a pathophysiological point of view, it is of interest that polymorphisms in genes of the WNT signalling system have been associated with the development of obesity and type 2 diabetes in humans. Moreover, recent findings indicate that certain WNT molecules are involved in the so-called low-grade inflammation of adipose tissue, which is crucial in the development of obesity-associated insulin resistance. These important findings in nutritional and metabolic medicine will be summarised in the present review.

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Section: Wnt Molecules In the Determination Of Preadipocytesmentioning

confidence: 99%

Role of WNT pathway in the determination of human mesenchymal stem cells into preadipocytes

Laudes¹

2011

Journal of Molecular Endocrinology

107

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“…Wnt signaling also suppresses the induction of Sox9, a key regulator of chondrogenesis, which results in the inhibition of mesenchymal stem cell differentiation to chondrocytes [14,15]. In addition, Wnt signaling upregulates two key regulators of myogenesis, MyoD and Myf 5, in the induction of myogenic differentiation [16].…”

Section: Introductionmentioning

confidence: 99%

Small molecule-based disruption of the Axin/β-catenin protein complex regulates mesenchymal stem cell differentiation

Gwak

Hwang

Park³

et al. 2011

Cell Res

108

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The Wnt/β-catenin pathway plays important roles in the differentiation of multiple cell types, including mesenchymal stem cells. Using a cell-based chemical screening assay with a synthetic chemical library of 270 000 compounds, we identified the compound SKL2001 as a novel agonist of the Wnt/β-catenin pathway and uncovered its molecular mechanism of action. SKL2001 upregulated β-catenin responsive transcription by increasing the intracellular β-catenin protein level and inhibited the phosphorylation of β-catenin at residues Ser33/37/Thr41 and Ser45, which would mark it for proteasomal degradation, without affecting CK1 and GSK-3β enzyme activities. Biochemical analysis revealed that SKL2001 disrupted the Axin/β-catenin interaction, which is a critical step for CK1-and GSK-3β-mediated phosphorylation of β-catenin at Ser33/37/Thr41 and Ser45. The treatment of mesenchymal stem cells with SKL2001 promoted osteoblastogenesis and suppressed adipocyte differentiation, both of which were accompanied by the activation of Wnt/β-catenin pathway. Our findings provide a new strategy to regulate mesenchymal stem cell differentiation by modulation of the Wnt/β-catenin pathway.

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“…Our previous studies have shown that Wnt3a induces myogenic differentiation in bone marrow MSCs via the ectopic expression of activated beta-catenin or pretreatment with Wnt3a conditioned medium in vitro [18,19] . In the current study, we hypothesized that Wnt3a would improve the myogenic differentiation efficiency of transplanted MSCs and repair the muscle damage in vivo.…”

Section: Acta Pharmacologica Sinica Npgmentioning

confidence: 99%

“…The medium was then collected, centrifuged at 1000×g for 10 min, and filtered through a nitrocellulose membrane. The abundance of the Wnt3a protein in Wnt3a-CM and L-CM was detected by Western blot analysis [19] . Wnt3a-CM was depleted of the Wnt3a protein by incubation with 4 μg/mL rabbit antiWnt3a antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA) at 4 °C overnight.…”

Section: Preparation Of Wnt3a-conditioned Mediummentioning

confidence: 99%

“…pGKWnt3a and pGKneo (control) plasmids were generously provided by Prof Shinji TAKADA (Okazaki Institute for Integrative Biosciences, National Institutes of Natural Sciences, Okazaki, Aichi, Japan). The Wnt3a-conditioned medium (Wnt3a-CM) and control L-conditioned medium (L-CM) were prepared as described previously [19,21] . Briefly, the L cells were transfected with pGKWnt3a or pGKneo plasmids with Lipofectamine 2000 according to the manufacturer's instructions (Invitrogen, Carlsbad, CA, USA).…”

Section: Preparation Of Wnt3a-conditioned Mediummentioning

confidence: 99%

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Activation of Wnt3a signaling promotes myogenic differentiation of mesenchymal stem cells in mdx mice

et al. 2016

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Aim: Duchenne muscular dystrophy (DMD) is an X-linked genetic muscular disorder with no effective treatment at present. Mesenchymal stem cell (MSC) transplantation has been used to treat DMD, but the efficiency is low. Our previous studies show that activation of Wnt3a signaling promotes myogenic differentiation of MSCs in vitro. Here we report an effective MSC transplantation therapy in mdx mice by activation of Wnt3a signaling. Methods: MSCs were isolated from mouse bone marrow, and pretreated with Wnt3a-conditioned medium (Wnt3a-CM), then transplanted into mdx mice. The recipient mice were euthanized at 4, 8, 12, 16 weeks after the transplantation, and muscle pathological changes were examined. The expression of dystrophin in muscle was detected using immunofluorescence staining, RT-PCR and Western blotting. Results: Sixteen weeks later, transplantation of Wnt3a-pretreated MSCs in mdx mice improved the characteristics of dystrophic muscles evidenced by significant reductions in centrally nucleated myofibers, the variability range of cross-sectional area (CSA) and the connective tissue area of myofibers. Furthermore, transplantation of Wnt3a-pretreated MSCs in mdx mice gradually and markedly increased the expression of dystrophin in muscle, and improved the efficiency of myogenic differentiation. Conclusion: Transplantation of Wnt3a-pretreated MSCs in mdx mice results in long-term amelioration of the dystrophic phenotype and restores dystrophin expression in muscle. The results suggest that Wnt3a may be a promising candidate for the treatment of DMD.

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Wnt3a signaling promotes proliferation, myogenic differentiation, and migration of rat bone marrow mesenchymal stem cells

Cited by 70 publications

References 41 publications

Role of WNT pathway in the determination of human mesenchymal stem cells into preadipocytes

Role of WNT pathway in the determination of human mesenchymal stem cells into preadipocytes

Small molecule-based disruption of the Axin/β-catenin protein complex regulates mesenchymal stem cell differentiation

Activation of Wnt3a signaling promotes myogenic differentiation of mesenchymal stem cells in mdx mice

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