β-catenin protein utilized by Tumour necrosis factor-α in porcine preadipocytes to suppress differentiation

Luο, Xingguang; Li, Huixia; Liu, Rongxin; Wu, Zongsong; Yang, Yingjuan; Yang, Gongshe

doi:10.5483/bmbrep.2009.42.6.338

Cited by 9 publications

(4 citation statements)

References 36 publications

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“…Enhanced Wnt/β‐catenin signaling either by Wnt overexpression or by deficiency of Wnt antagonists is associated with increased bone formation in mice and humans 34, 56. However, this mechanism is not consistent with our results, along with those of recent studies,43, 44 showing that activation of the canonical Wnt pathway inhibited osteogenic differentiation of human PDLSCs in inflammatory microenvironments. We provided evidence that a high level of β‐catenin significantly decreased the mRNA expression of Runx2 , Col1 , and Ocn in P‐PDLSCs.…”

Section: Discussioncontrasting

confidence: 93%

“…One of the major signal‐transduction pathways that have been associated with various stem cell attributes is the Wnt signaling pathway. Some recent studies showed that certain cytokines could influence the Wnt/β‐catenin signaling pathway in 3T3‐L1 preadipocytes 43–45. Thus we postulated that the inflammatory microenvironment would activate the Wnt/β‐catenin signaling pathway during the chronic inflammatory process.…”

Section: Resultsmentioning

confidence: 81%

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High levels of β-catenin signaling reduce osteogenic differentiation of stem cells in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway

Liu

Shi

Deng

et al. 2011

Journal of Bone and Mineral Research

176

170

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Periodontal ligament stem cells (PDLSCs), a new population of mesenchymal stem cells (MSCs), have been isolated from the periodontal ligament (PDL). The capacity of multipotency and self-renewal makes them an excellent cell source for bone regeneration and repair. However, their bone-regeneration ability could be awakened in inflammatory microenvironments, which may be the result of changes in their differentiation potential. Recently, genetic evidences has shown that the Wnt pathway plays an important role in bone homeostasis. In this study we have determined the specific role of b-catenin in osteogenic differentiation of PDLSCs obtained from inflammatory microenvironments (P-PDLSCs). The inflammatory microenvironment, while inhibiting osteogenic differentiation potential, promotes proliferation of MSCs. A higher the level of b-catenin in P-PDLSCs than in H-PDLSCs (PDLSCs obtained from a healthy microenvironment) resulted in the same disparity in canonical Wnt signaling pathway activation between each cell type. Here we show that activation of bcatenin suppresses the noncanonical Wnt/Ca 2þ pathway, leading to increased proliferation but reduced osteogenic differentiation of PPDLSCs. Downregulation of the levels of b-catenin by treatment with dickkopf-1 (DKK-1) leads to activation of the noncanonical Wnt/ Ca 2þ pathway, which, in turn, results in the promotion of osteogenic differentiation in P-PDLSCs. Interestingly, b-catenin can affect both the canonical Wnt/b-catenin pathway and the noncanonical Wnt/Ca 2þ pathway. Our data indicate that b-catenin plays a central role in regulating osteogenic differentiation of MSCs in inflammatory microenvironments. Given the important role of Wnt signaling in osteogenic differentiation, it is possible that agents that can modify this pathway may be of value in bone regeneration by MSCs in chronic inflammatory microenvironments. ß

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Section: Discussioncontrasting

confidence: 93%

Section: Resultsmentioning

confidence: 81%

High levels of β-catenin signaling reduce osteogenic differentiation of stem cells in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway

Liu

Shi

Deng

et al. 2011

Journal of Bone and Mineral Research

176

170

View full text Add to dashboard Cite

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“…Twenty to 90% of HCCs exhibit β-catenin activation, induced by diverse mechanisms, including mutations in the gene coding for β-catenin. Thus, inhibiting the Wnt/β-catenin pathway may constitute a target therapy for HCC (26). In this study, our results showed that the β-catenin inhibitor can reduce proliferation of the HCC cell line HepG2 via downregulation of β-catenin, and consequently, of its target gene iNOS.…”

Section: Discussionsupporting

confidence: 49%

FH535 inhibits the proliferation of HepG2 cells via downregulation of the Wnt/β-catenin signaling pathway

Liu

et al. 2014

Molecular Medicine Reports

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Hepatocellular carcinoma (HCC) is a primary cancer of the liver. Target therapy may improve prognosis of HCC. In the present study, we evaluated the inhibition of the Wnt/β-catenin pathway as a potential therapeutic approach. HepG2 cells were treated with the β-catenin inhibitor FH535. β-catenin protein expression was semi-quantitatively assessed using western blot analysis. Cell proliferation was examined with a 3‑(4,5-dimethyl-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay. The mRNA expression of nitric oxide synthase (iNOS) was detected by reverse transcription polymerase chain reaction. The Griess assay was used to determine nitric oxide (NO) concentration. FH535 inhibited the proliferation of HepG2 cells and decreased β-catenin protein expression. mRNA expression of iNOS, a target gene of the Wnt/β-catenin pathway, was decreased in FH535‑treated HepG2 cells compared to the control group. NO production was also reduced by FH535. In conclusion, the β-catenin inhibitor FH535 may inhibit HCC cell proliferation via downregulation of the Wnt/β-catenin pathway. Thus, targeting this pathway may be useful in HCC therapy.

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“…These authors postulate that VEGF upregulation could result from local tissue hypoxia from the growing fat pad (hypoxia activates HIF-1a, which in turn activates VEGF secretion by adipocytes and/or macrophage activation, leading to the release of cytokines and the generation of reactive oxygen species [ROS] and inflammation). With regard to b-catenin, we know that its function, in close association with Wnt, is to maintain preadipocytes in an undifferentiated state through PPARg inhibition (Luo et al 2009). When downregulated, however, b-catenin would drive preadipocyte differentiation and could also promote neoplastic transformation via its key role in cell-to-cell interactions (inhibition of contact theory; Kumar et al 2005).…”

Section: Mode Of Action Frameworkmentioning

confidence: 99%

The Development of Subcutaneous Sarcomas in Rodents Exposed to Peroxisome Proliferators Agonists

et al. 2012

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Peroxisome proliferator-activated receptors (PPARs) represent therapeutic targets for the management of type 2 diabetes mellitus and dyslipidemia. Rodent carcinogenicity studies have revealed a link between γ and dual γ/α PPAR agonist treatment and the increased incidence of subcutaneous (SC) liposarcomas/fibrosarcomas or hemangiosarcomas, but very little has been reported for potent and selective PPARα agonists. We present a mode of action framework for the development of SC mesenchymal tumors in rodents given PPAR agonists. (1) Tumor promotion results from pharmacologically mediated recruitment (proliferation and differentiation), thermogenesis and adipogenesis of stromovascular cells, and subsequent generation of oxidative free radicals. (2) Tumor initiation consists of chemotype-driven mitochondrial dysfunction causing uncontrolled oxidative stress and permanent DNA damage. Promotion is characterized by enhanced adipogenesis in the SC adipose tissue, where the baseline PPARγ expression and responsiveness to PPARγ ligands is the highest, and by thermogenesis through expression of the uncoupling protein 1 (UCP-1) and the PPARγ co-activator 1 α (PGC-1α), two factors more highly expressed in brown versus white adipose tissue. Initiation is supported by the demonstration of mitochondrial uncoupling and OXPHOS Complexes dysfunction (Complexes III, IV and V) by compounds associated with increased incidences of sarcomas (muraglitazar and troglitazone), but not others lacking malignant tumor effects (pioglitazone, rosiglitazone).

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β-catenin protein utilized by Tumour necrosis factor-α in porcine preadipocytes to suppress differentiation

Cited by 9 publications

References 36 publications

High levels of β-catenin signaling reduce osteogenic differentiation of stem cells in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway

High levels of β-catenin signaling reduce osteogenic differentiation of stem cells in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway

FH535 inhibits the proliferation of HepG2 cells via downregulation of the Wnt/β-catenin signaling pathway

The Development of Subcutaneous Sarcomas in Rodents Exposed to Peroxisome Proliferators Agonists

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