Developmental patterning in chondrocytic cultures by morphogenic gradients: BMP induces expression of <i>Indian hedgehog</i> and <i>Noggin</i>

Kameda, Takashi; Koike, Chika; Saitoh, Koichi; Kuroiwa, Atsushi; Iba, Hideo

doi:10.1046/j.1365-2443.1999.00250.x

Cited by 48 publications

(40 citation statements)

References 34 publications

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“…Similar findings have been observed with the application of N-terminal Sonic Hedgehog (Krishnan et al, 2001). Conversely, BMPs have been observed to induce Ihh expression in differentiating chondrocytes (Kameda et al, 1999;Macias et al, 1997;Minina et al, 2001). Our results show clearly that the loss of Ihh results in Bmp2/4 reduction in the calvarial bones.…”

Section: Relationship Between Ihh and Bone Morphogenetic Protein Signsupporting

confidence: 53%

Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling

Lenton

James

Manu

et al. 2011

Genesis

103

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Summary: Much is known regarding the role of Indian hedgehog (Ihh) in endochondral ossification, where Ihh regulates multiple steps of chondrocyte differentiation. The Ihh 2/2 phenotype is most notable for severely foreshortened limbs and a complete absence of mature osteoblasts. A far less explored phenotype in the Ihh 2/2 mutant is found in the calvaria, where bones form predominately through intramembranous ossification. We investigated the role of Ihh in calvarial bone ossification, finding that proliferation was largely unaffected. Instead, our results indicate that Ihh is a pro-osteogenic factor that positively regulates intramembranous ossification. We confirmed through histologic and quantitative gene analysis that loss of Ihh results in reduction of cranial bone size and all markers of osteodifferentiation. Moreover, in vitro studies suggest that Ihh loss reduces Bmp expression within the calvaria, an observation that may underlie the Ihh 2/2 calvarial phenotype. In conjunction with the newly recognized roles of Hedgehog deregulation in craniosynostosis, our study defines Ihh as an important positive regulator of cranial bone ossification.

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Section: Relationship Between Ihh and Bone Morphogenetic Protein Signsupporting

confidence: 53%

Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling

Lenton

James

Manu

et al. 2011

Genesis

103

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“…Smad signaling has negative feedback regulations at the cytoplasmic or nuclear level, which are important to restrict or terminate the biological effect of BMPs. There is also evidence that a negative feedback loop involving Noggin might account for the precise localization of BMP signaling (28). In addition, a number of BMP-2-responsive genes, known to promote bone formation, were identified.…”

Section: Discussionmentioning

confidence: 99%

Systematic assessment of the human osteoblast transcriptome in resting and induced primary cells

Grundberg

Brändström

Lam

et al. 2008

Physiological Genomics

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Osteoblasts are key players in bone remodeling. The accessibility of human primary osteoblast-like cells (HObs) from bone explants makes them a lucrative model for studying molecular physiology of bone turnover, for discovering novel anabolic therapeutics, and for mesenchymal cell biology in general. Relatively little is known about resting and dynamic expression profiles of HObs, and to date no studies have been conducted to systematically assess the osteoblast transcriptome. The aim of this study was to characterize HObs and investigate signaling cascades and gene networks with genomewide expression profiling in resting and bone morphogenic protein (BMP)-2- and dexamethasone-induced cells. In addition, we compared HOb gene expression with publicly available samples from the Gene Expression Omnibus. Our data show a vast number of genes and networks expressed predominantly in HObs compared with closely related cells such as fibroblasts or chondrocytes. For instance, genes in the insulin-like growth factor (IGF) signaling pathway were enriched in HObs ( P = 0.003) and included the binding proteins (IGFBP-1, -2, -5) and IGF-II and its receptor. Another HOb-specific expression pattern included leptin and its receptor ( P < 10−8). Furthermore, after stimulation of HObs with BMP-2 or dexamethasone, the expression of several interesting genes and pathways was observed. For instance, our data support the role of peripheral leptin signaling in bone cell function. In conclusion, we provide the landscape of tissue-specific and dynamic gene expression in HObs. This resource will allow utilization of osteoblasts as a model to study specific gene networks and gene families related to human bone physiology and diseases.

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“…Gremlin can bind to and inhibit BMP2 and BMP4, but does not interact with activin (Hsu et al 1998). Interestingly, expression of noggin and gremlin is enhanced by the very BMPs they act to inhibit, indicative of negative feedback loops in operation (Kameda et al 1999, Pereira et al 2000. In addition, certain isoforms of follistatin, noggin and chordin bind to cell-surface associated heparin-sulphate proteoglycans.…”

Section: Introductionmentioning

confidence: 99%

Granulosal and thecal expression of bone morphogenetic protein- and activin-binding protein mRNA transcripts during bovine follicle development and factors modulating their expression in vitro

Glister¹,

Satchell²,

Knight³

2011

Reproduction

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Evidence supports local roles for transforming growth factor b superfamily members including activins and bone morphogenetic proteins (BMP) in follicle development. Access of these ligands to signalling receptors is likely modulated by extracellular binding proteins (BP). In this study, we compared ex vivo expression of four BPs (chordin, gremlin, noggin and follistatin) in granulosal (GC) and theca interna (TC) compartments of developing bovine antral follicles (1-18 mm). Effects of FSH and IGF on BMP and BP expression by cultured GC, and effects of LH and BMPs on BP expression by cultured TC were also examined. Follicular expression of all four BP transcripts was higher in GC than TC compartments (P!0.001) a finding confirmed by immunohistochemistry. Follicle category affected (P!0.01) gremlin and follistatin mRNA abundance, with a significant cell-type!follicle category interaction for chordin, follistatin and noggin. Noggin transcript abundance was lower (P!0.05) in GC of large 'E-active' than 'E-inactive' follicles while follistatin mRNA level was higher (P!0.01). FSH enhanced CYP19, FSHR, INHBA and follistatin by GC without affecting BMP or BMP-BP expression. IGF increased CYP19 and follistatin, reduced BMP4, noggin and gremlin but did not affect chordin or FSHR mRNA levels. LH increased TC androgen secretion but had no effect on BMP or BP expression. BMPs uniformly suppressed TC androgen production whilst increasing chordin, noggin and gremlin mRNA levels up to 20-fold (P!0.01). These findings support the hypothesis that extracellular BP, mostly from GC, contribute to the regulation of intrafollicular BMP/activin signalling. Enhancement of thecal BP expression by BMP implies an autoregulatory feedback role to prevent excessive signalling.

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Developmental patterning in chondrocytic cultures by morphogenic gradients: BMP induces expression of Indian hedgehog and Noggin

Cited by 48 publications

References 34 publications

Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling

Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling

Systematic assessment of the human osteoblast transcriptome in resting and induced primary cells

Granulosal and thecal expression of bone morphogenetic protein- and activin-binding protein mRNA transcripts during bovine follicle development and factors modulating their expression in vitro

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