Trps1 deficiency enlarges the proliferative zone of growth plate cartilage by upregulation of Pthrp

Nishioka, K; Itoh, Shousaku; Suemoto, Hiroki; Kanno, Seiji; Gai, Zhibo; Kawakatsu, Motohisa; Tanishima, Hiroyuki; Morimoto, Yuuki; Hatamura, Ikuji; Yoshida, Munehito; Muragaki, Yasuteru

doi:10.1016/j.bone.2008.03.009

Cited by 33 publications

(25 citation statements)

References 23 publications

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“…In the long bones, Trps1 is expressed in periarticular chondrocytes, in presumptive joint mesenchyme and in prehypertrophic and terminal hypertrophic chondrocytes (Kunath et al 2002;Nishioka et al 2008). Trps1 is also expressed in the developing TMJ region throughout the embryonic stage.…”

Section: Discussionmentioning

confidence: 98%

Trps1 is necessary for normal temporomandibular joint development

et al. 2012

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Mutation of the human TRPS1 gene leads to trichorhinophalangeal syndrome (TRPS), which is characterized by an abnormal development of various organs including the craniofacial skeleton. Trps1 has recently been shown to be expressed in the jaw joints of zebrafish; however, whether Trps1 is expressed in the mammalian temporomandibular joint (TMJ), or whether it is necessary for TMJ development is unknown. We have analyzed (1) the expression pattern of Trps1 during TMJ development in mice and (2) TMJ development in Trps1 knockout animals. Trps1 is expressed in the maxillo-mandibular junction at embryonic day (E) 11.5. At E15.5, expression is restricted to the developing condylar cartilage and to the surrounding joint disc progenitor cells. In Trps1 knockout mice, the glenoid fossa of the temporal bone forms relatively normally but the condylar process is extremely small and the joint disc and cavities do not develop. The initiation of condyle formation is slightly delayed in the mutants at E14.5; however, at E18.5, the flattened chondrocyte layer is narrowed and most of the condylar chondrocytes exhibit precocious chondrocyte maturation. Expression of Runx2 and its target genes is expanded toward the condylar apex in the mutants. These observations underscore the indispensable role played by Trps1 in normal TMJ development in supporting the differentiation of disc and synoviocyte progenitor cells and in coordinating condylar chondrocyte differentiation.

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Section: Discussionmentioning

confidence: 98%

Trps1 is necessary for normal temporomandibular joint development

et al. 2012

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“…Also, we reported previously that Trps1 directly binds to the GATA sites of the promoters of the Stat3 and Pthrp genes, thereby regulating the proliferation or apoptosis of chondrocytes and the length of the epiphyseal cartilage, respectively 2,34 ; however, the downstream target genes of Trps1 involved in renal development have not yet been examined. Given that Trps1 is a transcriptional repressor, 35 it seems possible that it negatively regulates a transcription factor that suppresses Ecadherin expression, such as Snail.…”

Section: Discussionmentioning

confidence: 99%

Trps1 Functions Downstream of Bmp7 in Kidney Development

Gai¹,

Zhou²,

Itoh³

et al. 2009

Journal of the American Society of Nephrology

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During embryonic development, the mesenchyme of the lungs, gut, kidneys, and other tissues expresses Trps1, an atypical member of the GATA-type family of transcription factors. Our previous work suggested the possibility that Trps1 acts downstream of bone morphogenic protein 7 (Bmp7), which is essential for normal renal development. To examine the role of Trps1 during early renal development, we generated Trps1-deficient mice and examined their renal histology. Compared with wild-type mice, Trps1-deficient newborn mice had fewer tubules and glomeruli, an expanded renal interstitium, and numerous uninduced metanephric mesenchymal cells, which resulted in fewer nephrons. In wild-type kidneys, Trps1 expression was present in ureteric buds, cap mesenchyme, and renal vesicles, whereas Trps1 was virtually absent in Bmp7-deficient kidneys. Furthermore, Trps1-deficient kidneys had low levels of Pax2 and Wt1, which are markers of condensed mesenchymal cells, suggesting that a lack of Trps1 affects the differentiation of cap mesenchyme to renal vesicles. In cultured metanephric mesenchymal cells, Bmp7 induced Trps1 and E-cadherin and downregulated vimentin. Knockdown of Trps1 with small interference RNA inhibited this Bmp7-induced mesenchymal-to-epithelial transition. Last, whole-mount in situ hybridization of Wnt9b and Wnt4 demonstrated prolonged branching of ureteric buds and sparse cap mesenchyme in the kidneys of Trps1-deficient mice. Taken together, these findings suggest that normal formation of nephrons requires Trps1, which mediates mesenchymal-to-epithelial transition and ureteric bud branching during early renal development.

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“…Expression of PTHrP by growth plate chondrocytes is inhibited by TRPS1, as demonstrated by studies in TRPS1-null mice and accompanying in vitro studies (Nishioka et al 2008). Mice with a heterozygous in-frame deletion of the DNA-binding domain of TRPS1 show elevated expression of RUNX2 in the growth plate; moreover, TRPS1 directly interacts with RUNX2 to inhibit its function (Napierala et al 2008).…”

Section: Hypertrophymentioning

confidence: 97%

The skeleton: a multi-functional complex organ. The growth plate chondrocyte and endochondral ossification

Mackie¹,

Tatarczuch²,

Mirams³

2011

Journal of Endocrinology

368

319

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Endochondral ossification is the process that results in both the replacement of the embryonic cartilaginous skeleton during organogenesis and the growth of long bones until adult height is achieved. Chondrocytes play a central role in this process, contributing to longitudinal growth through a combination of proliferation, extracellular matrix (ECM) secretion and hypertrophy. Terminally differentiated hypertrophic chondrocytes then die, allowing the invasion of a mixture of cells that collectively replace the cartilage tissue with bone tissue. The behaviour of growth plate chondrocytes is tightly regulated at all stages of endochondral ossification by a complex network of interactions between circulating hormones (including GH and thyroid hormone), locally produced growth factors (including Indian hedgehog, WNTs, bone morphogenetic proteins and fibroblast growth factors) and the components of the ECM secreted by the chondrocytes (including collagens, proteoglycans, thrombospondins and matrilins). In turn, chondrocytes secrete factors that regulate the behaviour of the invading bone cells, including vascular endothelial growth factor and receptor activator of NFkB ligand. This review discusses how the growth plate chondrocyte contributes to endochondral ossification, with some emphasis on recent advances.

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Trps1 deficiency enlarges the proliferative zone of growth plate cartilage by upregulation of Pthrp

Cited by 33 publications

References 23 publications

Trps1 is necessary for normal temporomandibular joint development

Trps1 is necessary for normal temporomandibular joint development

Trps1 Functions Downstream of Bmp7 in Kidney Development

The skeleton: a multi-functional complex organ. The growth plate chondrocyte and endochondral ossification

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