Regulation and role of Sox9 in cartilage formation

Healy, Chris; Uwanogho, Dafe; Sharpe, Paul T.

doi:10.1002/(sici)1097-0177(199905)215:1<69::aid-dvdy8>3.0.co;2-n

Cited by 200 publications

(93 citation statements)

References 30 publications

(20 reference statements)

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“…We utilized degenerate RT-PCR on purifi ed day 6 male gonad RNA using generic Sry-type HMG box primers to generate fragments for cloning into a plasmid vector. Twenty independent clones were sequenced, revealing that 12 clones were cSox4 [45], 7 were cSox11 [46] and 1 was cSox9 [47]. One possible explanation for these results is that the degenerate primers used show a bias for amplifi cation of cSox4 and cSox11 templates.…”

Section: Resultsmentioning

confidence: 99%

Regulation of Amh during sex determination in chickens: Sox gene expression in male and female gonads

Takada

Mano

Koopman

2005

Cell. Mol. Life Sci.

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A master sex-determining gene, the Y chromosome-linked anti-Müllerian hormone (amhy) gene, has been described in two New World atheriniform species but little is known on the distribution, evolution, and function(s) of this gene in other Atheriniformes. Interestingly, amhy has been found to coexist with temperature-dependent sex determination (TSD), providing a unique opportunity to explore the interplay between genotypic and environmental sex determination. In this study, the search for an amhy homolog was extended to an Old World atheriniform, the cobaltcap silverside Hypoatherina tsurugae (Atherinidae). The full sequences, including the coding and noncoding regions, of the autosomal amh (amha) and a putative amhy were obtained. The deduced Amha and Amhy proteins comprised 511 and 340 amino acids (aa), respectively. PCR analysis with genomic DNA from wild adults and from laboratory-reared juveniles revealed a high, but not complete association of 95% between amhy and maleness. The spatiotemporal expression of amhy and amha during gonadal sex differentiation was analyzed by qRT-PCR and in situ hybridization (ISH). amhy transcription (in amhy-positive larvae) started before and peaked during histological differentiation of the gonads whereas amha was negligible during the same period in both genotypes. These results demonstrate that the amhy, although with some structural differences in relation to the amhy of some New World atheriniforms, is strongly associated with maleness and probably important for testicular development in this Old World atheriniform. Thus, amhy is a candidate sex determination gene in cobaltcap silverside and it will be key to scrutinize the mechanism of sex determination in this species. KEYWORDS

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Section: Resultsmentioning

confidence: 99%

Regulation of Amh during sex determination in chickens: Sox gene expression in male and female gonads

Takada

Mano

Koopman

2005

Cell. Mol. Life Sci.

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“…It has been observed that growth factors such as FGF-2 and BMP-2 which can promote (re)differentiation (Denker et al 1999;Martin et al 1999) increase the expression of transcription factor sox9 (EnomotoIwamoto et al 1998;Healy et al 1999;Zehentner et al 1999). Activation of sox9 gene seems to be mediated by mitogen-activated protein kinase (MAPK) pathway de Crombrugghe et al 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Sox9 promotes the expression of chondrocyte marker genes (Zehentner et al 1999) and is required for the initiation of cartilage differentiation during embryogenesis. The gene sox9 was found to be activated in chondrogenic condensations during chondrogenesis in mice (Wright et al 1995;Ng et al 1997;Healy et al 1999) and might also control expression of cell surface proteins essential for mesenchymal condensations . Sox9 is also expressed in high-density cultures (Kulyk et al 2000) and may be important for redifferentiation of dedifferentiated chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

Redifferentiation of dedifferentiated human chondrocytes in high-density cultures

Schulze‐Tanzil

Souza

Castrejón

et al. 2002

Cell and Tissue Research

187

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High-density cultures are widely used as an in vitro model for studies of embryonic cartilage formation. In the present study we investigated the suitability of high-density cultures for the redifferentiation of dedifferentiated chondrocytes. When primary human chondrocytes were cultured in alginate beads, some cells emigrated into Petri dishes. These cells were cultured for one to eight passages (each passage lasting about 3 days) in monolayer culture. At each passage, monolayer cells were removed and allowed to grow in high-density cultures at the medium-air interface and subsequently investigated with morphological, immunolocalization and biochemical methods for the production of cartilage-specific markers, i.e. collagen type II and cartilage-specific proteoglycans. When such dedifferentiated chondrocytes from monolayer passages P1-P4 were introduced in high-density culture, they regained a chondrocyte phenotype and formed cartilage nodules surrounded by fibroblast-like cells. Cells were interconnected by typical gap junctions and after a few days in culturing produced cartilage-specific extracellular matrix, notably collagen type II and cartilage-specific proteoglycans. In contrast, cells taken from monolayer passages P5-P8 did not produce these chondrocyte-specific extracellular materials when grown in high-density culture. We conclude that the growth of dedifferentiated chondrocytes in high-density culture promotes their redifferentiation and reveals their chondrogenic potential. Such high-density cultures might serve as a model system to initiate and promote the redifferentiation of chondrocytes and to provide sufficient quantities of differentiated chondrocytes for autologous chondrocyte transplantation.

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“…However, Sox9 has been shown to be required, and the forced expression of Brachyury appears to mediate the onset of chondrogenesis that is dependent upon fibroblast growth factor 3 receptor in mesenchymal stem cells (Hoffmann et al 2002;Healy et al 1999). Our group has previously suggested that the helix-loop-helix (HLH) protein Id1 (inhibitor of DNA binding/differentiation 1) is involved in the control of proliferation and differentiation of cartilage (Asp et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Notch and HES5 are regulated during human cartilage differentiation

et al. 2006

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The molecular mechanisms of cartilage differentiation are poorly understood. In a variety of tissues other than cartilage, members of the basic helix-loop-helix (bHLH) family of transcription factors have been demonstrated to play critical roles in differentiation. We have characterized the human bHLH gene HES5 and investigated its role during chondrogenesis. Blockage of the Notch signaling pathway with a gamma-secretase inhibitor has demonstrated that the human HES5 gene is a downstream marker of Notch signaling in articular chondrocytes. Markers for the Notch signaling pathway significantly decrease during cartilage differentiation in vitro. Cell proliferation assayed by using BrdU has revealed that blockage of Notch signaling is associated with significantly decreased proliferation. Northern blot and reverse transcription/polymerase chain reaction of a panel of various tissues have shown that HES5 is transcribed as a 5.4-kb mRNA that is ubiquitously expressed in diverse fetal and adult tissues. Articular cartilage from HES5(-/-) and wild-type mice has been analyzed by using various histological stains. No differences have been detected between the wild-type and HES5(-/-) mice. Our data thus indicate that the human HES5 gene is coupled to the Notch receptor family, that expression of Notch markers (including HES5) decreases during cartilage differentiation, and that the blockage of Notch signaling is associated with significantly decreased cell proliferation.

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Regulation and role of Sox9 in cartilage formation

Cited by 200 publications

References 30 publications

Regulation of Amh during sex determination in chickens: Sox gene expression in male and female gonads

Regulation of Amh during sex determination in chickens: Sox gene expression in male and female gonads

Redifferentiation of dedifferentiated human chondrocytes in high-density cultures

Notch and HES5 are regulated during human cartilage differentiation

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