Expression of Thyroid Hormone Receptor Isoforms in Rat Growth Plate Cartilage In Vivo

Ballock, R. Tracy; Mita, Barry C.; Zhou, Xiaolan; Chen, Daniel H.-C.; Mink, Lynn M.

doi:10.1359/jbmr.1999.14.9.1550

Cited by 46 publications

(21 citation statements)

References 49 publications

(70 reference statements)

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“…In contrast, combining some of the TR mutations results in a profound disruption of these processes, revealing functional redundancies between TR isoforms. One redundancy clearly occurs with TR␣1 and TR␤, which are both expressed in bone (2,5,31,34) and which in combined but not individual knockouts result in bone maturation delay. The selective abolishing of TR␣1 in TR␣1 Ϫ/Ϫ mice does not result in obvious impairment of linear growth or bone maturation.…”

Section: Tr␣1 and Tr␤s Cooperate To Regulate Tsh Productionmentioning

confidence: 99%

Genetic Analysis Reveals Different Functions for the Products of the Thyroid Hormone Receptor α Locus

Gauthier¹,

Plateroti²,

Harvey

et al. 2001

Molecular and Cellular Biology

243

166

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Thyroid hormone receptors are encoded by the TR␣ (NR1A1) and TR␤ (NR1A2) loci. These genes are transcribed into multiple variants whose functions are unclear. Analysis by gene inactivation in mice has provided new insights into the functional complexity of these products. Different strategies designed to modify the TR␣ locus have led to strikingly different phenotypes. In order to analyze the molecular basis for these alterations, we generated mice devoid of all known isoforms produced from the TR␣ locus (TR␣ 0/0 ). These mice are viable and exhibit reduced linear growth, bone maturation delay, moderate hypothermia, and reduced thickness of the intestinal mucosa. Compounding TR␣ 0 and TR␤ ؊ mutations produces viable TR␣ 0/0 ␤ ؊/؊ mice, which display a more severe linear growth reduction and a more profound hypothermia as well as impaired hearing. A striking phenotypic difference is observed between TR␣ 0/0 and the previously described TR␣ ؊/؊ mice, which retain truncated TR⌬␣ isoforms arising from a newly described promoter in intron 7. The lethality and severe impairment of the intestinal maturation in TR␣ ؊/؊ mice are rescued in TR␣ 0/0 animals. We demonstrate that the TR⌬␣ protein isoforms, which are natural products of the TR␣ locus, are the key determinants of these phenotypical differences. These data reveal the functional importance of the non-T3-binding variants encoded by the TR␣ locus in vertebrate postnatal development and homeostasis.

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Section: Tr␣1 and Tr␤s Cooperate To Regulate Tsh Productionmentioning

confidence: 99%

Genetic Analysis Reveals Different Functions for the Products of the Thyroid Hormone Receptor α Locus

Gauthier¹,

Plateroti²,

Harvey

et al. 2001

Molecular and Cellular Biology

243

166

View full text Add to dashboard Cite

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“…3). TR-␣1, -␣2, and -␤1 mRNA and -␣1 and -␤1 proteins have been identified in rat growth plate by reverse transcriptase PCR and Western blotting (122). High-affinity nuclear T3 binding sites are present in human fetal epiphyseal chondrocytes (123) and TR-␣1, -␣2, and -␤1 proteins have been identified in chondrocytes at sites of endochondral ossification (124).…”

Section: Hormone Action In Skeletal Cellsmentioning

confidence: 99%

Interactions between GH, IGF-I, Glucocorticoids, and Thyroid Hormones during Skeletal Growth

et al. 2002

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“…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 [Lanske et al, 1996[Lanske et al, , 1999Serra et al, 1997;Enomoto-Iwamoto et al, 1998;Ballock et al, 1999;Ferguson et al, 2000;Yang et al, 2001;Li et al, 2003]. …”

mentioning

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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Expression of Thyroid Hormone Receptor Isoforms in Rat Growth Plate Cartilage In Vivo

Cited by 46 publications

References 49 publications

Genetic Analysis Reveals Different Functions for the Products of the Thyroid Hormone Receptor α Locus

Genetic Analysis Reveals Different Functions for the Products of the Thyroid Hormone Receptor α Locus

Interactions between GH, IGF-I, Glucocorticoids, and Thyroid Hormones during Skeletal Growth

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

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