Smad1 plays an essential role in bone development and postnatal bone formation

Wang, M.; Jin, Hongting; Tang, De Zhi; Huang, Shixia; Zuscik, Michael J.; Chen, D.

doi:10.1016/j.joca.2011.03.004

Cited by 54 publications

(49 citation statements)

References 43 publications

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“…Osteoblast-specific Smad1 gene knockout mice present with impaired postnatal bone formation (35). So far, several miRNAs have been reported to target Smad1 and regulate its expression in different physiologic conditions.…”

Section: Discussionmentioning

confidence: 99%

miR-30 Family Members Negatively Regulate Osteoblast Differentiation

Wu¹,

Zhou

Hong

et al. 2012

Journal of Biological Chemistry

170

125

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Background: microRNAs (miRNAs) are closely related to osteogenesis. Results: miR-30 family members (miR-30a, -30b, -30c, and -30d) mediate the inhibition of osteogenesis by targeting Smad1 and Runx2. Conclusion: miR-30 family members are key negative regulators of BMP-2-mediated osteogenic differentiation. Significance: These findings may provide new insights into understanding the regulatory role of miRNAs in the process of osteogenic differentiation.

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Section: Discussionmentioning

confidence: 99%

miR-30 Family Members Negatively Regulate Osteoblast Differentiation

Wu¹,

Zhou

Hong

et al. 2012

Journal of Biological Chemistry

170

125

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“…Smad1 is a critical immediate downstream mediator of BMP receptor transduction [51,52]. Chondrocyte-specific and osteoblast-specific Smad1 conditional knockout mice were bred to assess postnatal bone formation [51].…”

Section: Bmp Knockout Phenotypesmentioning

confidence: 99%

“…Chondrocyte-specific and osteoblast-specific Smad1 conditional knockout mice were bred to assess postnatal bone formation [51]. Chondrocyte-specific deletion of the Smad1 gene resulted in delayed calvarial bone development.…”

Section: Bmp Knockout Phenotypesmentioning

confidence: 99%

BMP signaling in mesenchymal stem cell differentiation and bone formation

Beederman¹,

Lamplot²,

Guo³

et al. 2013

JBiSE

250

203

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Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily and have diverse functions during development and organogenesis. BMPs play a major role in skeletal development and bone formation, and disruptions in BMP signaling cause a variety of skeletal and extraskeletal anomalies. Several knockout models have provided insight into the mechanisms responsible for these phenotypes. Proper bone formation requires the differentiation of osteoblasts from mesenchymal stem cell (MSC) precursors, a process mediated in part by BMP signaling. Multiple BMPs, including BMP2, BMP6, BMP7 and BMP9, promote osteoblastic differentiation of MSCs both in vitro and in vivo. BMP9 is one of the most osteogenic BMPs yet is a poorly characterized member of the BMP family. Several studies demonstrate that the mechanisms controlling BMP9-mediated osteogenesis differ from other osteogenic BMPs, but little is known about these specific mechanisms. Several pathways critical to BMP9-mediated osteogenesis are also important in the differentiation of other cell lineages, including adipocytes and chondrocytes. BMP9 has also demonstrated translational promise in spinal fusion and bone fracture repair. This review will summarize our current knowledge of BMP-mediated osteogenesis, with a focus on BMP9, by presenting recently completed work which may help us to further elucidate these pathways.

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“…Previous studies have demonstrated that Smads1, −4 and −5 are required for skeletogenesis (Retting et al, 2009; Tan et al, 2007). Osteoblast-specific Smad1 or Smad4 mutants showed decreased bone formation (Tan et al, 2007; Wang et al, 2011). As expected, heterozygous null mutation of Bmpr1b resulted in 50% reduction of Bmpr1b expression in ca1A;1bH and Bmpr1b +/− (Fig.…”

Section: Discussionmentioning

confidence: 99%

BmpR1A is a major type 1 BMP receptor for BMP-Smad signaling during skull development

Pan

Zhang

Abraham

et al. 2017

Developmental Biology

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Craniosynostosis is caused by premature fusion of one or more sutures in an infant skull, resulting in abnormal facial features. The molecular and cellular mechanisms by which genetic mutations cause craniosynostosis are incompletely characterized, and many of the causative genes for diverse types of syndromic craniosynostosis have not yet been identified. We previously demonstrated that augmentation of BMP signaling mediated by a constitutively active BMP type IA receptor (ca-BmpR1A) in neural crest cells (ca1A hereafter) causes craniosynostosis and superimposition of heterozygous null mutation of Bmpr1a rescues premature suture fusion (ca1A;1aH hereafter). In this study, we superimposed heterozygous null mutations of the other two BMP type I receptors, Bmpr1b and Acvr1 (ca1A;1bH and ca1A;AcH respectively hereafter) to further dissect involvement of BMP-Smad signaling. Unlike caA1;1aH, ca1A;1bH and ca1A;AcH did not restore the craniosynostosis phenotypes. In our in vivo study, Smad-dependent BMP signaling was decreased to normal levels in mut;1aH mice. However, BMP receptor-regulated Smads (R-Smads; pSmad1/5/9 hereafter) levels were comparable between ca1A, ca1A;1bH and ca1A;AcH mice, and elevated compared to control mice. Bmpr1a, Bmpr1b and Acvr1 null cells were used to examine potential mechanisms underlying the differences in ability of heterozygosity for Bmpr1a vs. Bmpr1b or Acvr1 to rescue the mut phenotype. pSmad1/5/9 level was undetectable in Bmpr1a homozygous null cells while pSmad1/5/9 levels did not decrease in Bmpr1b or Acvr1 homozygous null cells. Taken together, our study indicates that different levels of expression and subsequent activation of Smad signaling differentially contribute each BMP type I receptor to BMP-Smad signaling and craniofacial development. These results also suggest differential involvement of each type 1 receptor in pathogenesis of syndromic craniosynostoses.

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Smad1 plays an essential role in bone development and postnatal bone formation

Cited by 54 publications

References 43 publications

miR-30 Family Members Negatively Regulate Osteoblast Differentiation

miR-30 Family Members Negatively Regulate Osteoblast Differentiation

BMP signaling in mesenchymal stem cell differentiation and bone formation

BmpR1A is a major type 1 BMP receptor for BMP-Smad signaling during skull development

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