AP-1 Transcription Factor Complex Is a Target of Signals from Both WNT-7a and N-Cadherin-Dependent Cell–Cell Adhesion Complex during the Regulation of Limb Mesenchymal Chondrogenesis

Tufan, A. Çevik; Daumer, Kathleen M.; DeLise, Anthony M.; Tuan, Rocky S.

doi:10.1006/excr.2001.5448

Cited by 55 publications

(43 citation statements)

References 24 publications

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“…Moreover, because the previous studies showed that TGF-ß1 treatment was able to activate gene expressions of c-Jun and c-Fos [49][50][51], TGF-ß1 upregulation by dynamic compression loading may be able to mediate transcription of c-Fos and c-Jun through feedback mechanism. Furthermore, because previous studies indicated that activity of the AP-1 complex may play an important role in regulating chondrocyte differentiation of chondrogenic cell lines [28,30] and limb mesenchymal cells [29] as well as TGF-ß-induced type II collagen expression in chondrocytes [52], our finding also suggests that dynamic compressive loading may promote chondrogenic gene expressions of BMMSCs through activation of the AP-1 complex.…”

Section: Discussionsupporting

confidence: 57%

Temporal Expression Patterns and Corresponding Protein Inductions of Early Responsive Genes in Rabbit Bone Marrow–Derived Mesenchymal Stem Cells Under Cyclic Compressive Loading

2005

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Our recent study suggested that cyclic compressive loading may promote chondrogenesis of rabbit bone-marrow mesenchymal stem cells (BM-MSCs) in agarose cultures through the transforming growth factor (TGF)-β signaling pathway. It has been shown that the activating protein 1 (AP-1) (JunFos) complex mediated autoinduction of TGF-ß1 and its binding activity was essential for promoting chondrogenesis of mesenchymal cells, whereas Sox9 was identified as an essential transcription factor for chondrogenesis of embryonic mesenchymal cells. The objective of this study was to examine temporal expression patterns of early responsive genes (Sox9, c-Fos, c-Jun, and TGF-ß type Ι and II receptors) and induction of their corresponding proteins in agarose culture of rabbit BM-MSCs subjected to cyclic compressive loading. The rabbit BM-MSCs were obtained from the tibias and femurs of New Zealand White rabbits. Cell-agarose constructs were made by suspending BM-MSCs in 2% agarose gel (10 7 cells/ml) for cyclic, unconfined compression tests performed in a custommade bioreactor. In the loading experiment, specimens were subjected to sinusoidal loading with a magnitude of 15% strain at a frequency of 1 hertz for 4 hours per day. Experiments were conducted for 2 consecutive days. This study showed that cyclic compressive loading promoted gene expressions of Sox9, cJun, and both TGF-ß receptors and productions of their corresponding proteins, whereas those gene expressions exhibited different temporal expression patterns among genes and between 2 days of testing. The gene expression of c-Fos was detected only in the samples subjected to 1-hour dynamic compressive loading. These findings suggest that the TGF-ß signal transduction and activities of AP-1 and Sox9 are involved in the early stage of BM-MSC chondrogenesis promoted by dynamic compressive loading.

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Section: Discussionsupporting

confidence: 57%

Temporal Expression Patterns and Corresponding Protein Inductions of Early Responsive Genes in Rabbit Bone Marrow–Derived Mesenchymal Stem Cells Under Cyclic Compressive Loading

2005

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“…Wnt1, Wnt4, and Wnt7a have been shown to block chondrogenesis [Rudnicki and Brown, 1997;Church et al, 2002;Tufan et al, 2002]. In contrast, overexpression of Wnt3a [Fischer et al, 2002], Wnt5a, and Wnt5b enhance chondrogenesis .…”

Section: Discussionmentioning

confidence: 99%

Wnt‐mediated regulation of chondrocyte maturation: Modulation by TGF‐β

Dong

Drissi

Chen

et al. 2005

J of Cellular Biochemistry

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Wnt proteins are expressed during limb morphogenesis, yet their role and mechanism of action remains unclear during long bone growth. Wnt expression, effects and modulation of signaling events by BMP and transforming growth factor-beta (TGF-β) were evaluated in chick embryonic chondrocytes. Chondrocyte cell cultures underwent spontaneous maturation with increased expression of colX and this was associated with an increase in the expression of multiple Wnts, including Wnts 4, 5a, 8c, and 9a. Both parathyroid hormone related peptide (PTHrP) and TGF-β inhibited colX, but had disparate effects on Wnt expression. While TGF-β strongly inhibited all Wnts, PTHrP did not inhibit either Wnt8c or Wnt9a and had lesser effects on the expression of the other Wnts. BMP-2 induced colX expression, and also markedly increased Wnt8c expression. Overexpression of β-Catenin and/or T cell factor (TCF)-4 also induced the type X collagen promoter. Overexpression of Wnt8c induced maturation, as did overexpression of β-Catenin. The Wnt8c/β-Catenin maturational effects were enhanced by BMP-2 and inhibited by TGF-β. TGF-β also inhibited activation of the Topflash reporter by β-Catenin, suggesting a direct inhibitory effect since the Topflash reporter contains only β-Catenin binding sequences. In turn β-Catenin inhibited activation of the p3TP-Luc reporter by TGF-β, although the effect was partial. Thus, Wnt/β-Catenin signaling is a critical regulator of the rate of chondrocyte differentiation. Moreover, this pathway is modulated by members of the TGF-β family and demonstrates the highly integrated nature of signals controlling endochondral ossification. J. Cell. Biochem. KeywordsWnt; Chondrocyte; β-Catenin; TGF-βtype X collagen Longitudinal bone growth is a highly regulated process in which chondrocytes complete sequential stages of proliferation, maturation, and hypertrophy marked by a 10-fold increase in type X collagen, and expression of alkaline phosphatase [Hunziker, 1994;Johnson and Tabin, 1997]. Local and systemic factors regulate chondrocyte maturation, and act through multiple independent signaling pathways. Several factors are known to influence the rate of chondrocyte differentiation. Transforming growth factor-beta (TGF-β) and parathyroid hormone related peptide (PTHrP) slow the rate of chondrocyte maturation, while bone morphogenetic proteins (BMPs), thyroid hormone, and retinoic acid stimulate terminal differentiation

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“…20,21 Oxidative stress and tissue GSH stores can modulate activation of the redox-sensitive transcription factors AP-1 and nuclear factor B, which regulate chondrogenesis. 2,[37][38][39] In addition, degradation of GSH stores by ␥-glutamyl transpeptidase critically supports intracellular levels of cysteine, a requisite mechanism to maintain endochondral chondrocyte proliferation. 21 In this study, free cysteamine alone induced sulfated proteoglycans synthesis and collagen II expression in wildtype MSCs, elevating collagen II expression in pellet culture in wild-type MSCs to levels comparable to those in cultured ank/ank MSCs without cysteamine treatment.…”

Section: (K Johnson Et Al Unpublished Observations)mentioning

confidence: 99%

Vanin-1 Pantetheinase Drives Increased Chondrogenic Potential of Mesenchymal Precursors in ank/ank Mice

Johnson

Yao

Lane

et al. 2008

The American Journal of Pathology

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Widespread endochondral and intramembranous ectopic bone formation is mediated by extracellular PP i deficiency that develops in ank/ank mice. Herein we report on the rapid condensation into chondrogenic nodules of cultured ank/ank bone marrow stromal cells (BMSCs). We compared the roles of increased chondrogenic potential versus altered osteoblast function in the ank/ank phenotype. To do so, we crossbred ank/ank mice with mice lacking Vanin-1 pantetheinase, which inhibits synthesis of the chondrogenesis regulator glutathione, since we observed increased Vanin-1 expression and pantetheinase activity and decreased glutathione in ank/ank BMSCs.

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AP-1 Transcription Factor Complex Is a Target of Signals from Both WNT-7a and N-Cadherin-Dependent Cell–Cell Adhesion Complex during the Regulation of Limb Mesenchymal Chondrogenesis

Cited by 55 publications

References 24 publications

Temporal Expression Patterns and Corresponding Protein Inductions of Early Responsive Genes in Rabbit Bone Marrow–Derived Mesenchymal Stem Cells Under Cyclic Compressive Loading

Temporal Expression Patterns and Corresponding Protein Inductions of Early Responsive Genes in Rabbit Bone Marrow–Derived Mesenchymal Stem Cells Under Cyclic Compressive Loading

Wnt‐mediated regulation of chondrocyte maturation: Modulation by TGF‐β

Vanin-1 Pantetheinase Drives Increased Chondrogenic Potential of Mesenchymal Precursors in ank/ank Mice

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