GNAS locus: bone related diseases and mouse models

Yang, Wan; Zuo, Yiyi; Zhang, Nuo; Wang, Kangning; Zhang, Runze; Chen, Ziyi; He, Qing

doi:10.3389/fendo.2023.1255864

Cited by 3 publications

(2 citation statements)

References 143 publications

(174 reference statements)

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“…Then, our study shows that (1) GNAS haploinsufficiency alone induces osteodifferentiation of NI cells, and (2) the simultaneous presence of induction accelerates the process towards an OS-like phenotype. Our data confirm the already-known role of Gsa in preventing ectopic osteoblastogenesis due to its crucial role in orchestrating the Wnt and Hh signaling pathways (52). Gsa enhances the canonical Wnt pathway, promoting the MSC progenitor to enter the OB lineage and inhibiting its complete differentiation and all OBs already channeled into the osteoblastic lineage.…”

Section: Discussionsupporting

confidence: 87%

Targeted silencing of GNAS in a human model of osteoprogenitor cells results in the deregulation of the osteogenic differentiation program

Elli,

Mattinzoli,

Ikehata

et al. 2024

Front. Endocrinol.

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IntroductionThe dysregulation of cell fate toward osteoprecursor cells associated with most GNAS-based disorders may lead to episodic de novo extraskeletal or ectopic bone formation in subcutaneous tissues. The bony lesion distribution suggests the involvement of abnormal differentiation of mesenchymal stem cells (MSCs) and/or more committed precursor cells. Data from transgenic mice support the concept that GNAS is a crucial factor in regulating lineage switching between osteoblasts (OBs) and adipocyte fates. The mosaic nature of heterotopic bone lesions suggests that GNAS genetic defects provide a sensitized background for ectopic osteodifferentiation, but the underlying molecular mechanism remains largely unknown.MethodsThe effect of GNAS silencing in the presence and/or absence of osteoblastic stimuli was evaluated in the human L88/5 MSC line during osteodifferentiation. A comparison of the data obtained with data coming from a bony lesion from a GNAS-mutated patient was also provided.ResultsOur study adds some dowels to the current fragmented notions about the role of GNAS during osteoblastic differentiation, such as the premature transition of immature OBs into osteocytes and the characterization of the differences in the deposed bone matrix.ConclusionWe demonstrated that our cell model partially replicates the in vivo behavior results, resulting in an applicable human model to elucidate the pathophysiology of ectopic bone formation in GNAS-based disorders.

show abstract

Section: Discussionsupporting

confidence: 87%

Targeted silencing of GNAS in a human model of osteoprogenitor cells results in the deregulation of the osteogenic differentiation program

Elli,

Mattinzoli,

Ikehata

et al. 2024

Front. Endocrinol.

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show abstract

“…Biological processes influenced by Gv include oviposition, hatching, and craniofacial development. Pleiotropic effects such as these are characteristic for knockouts of other G alpha proteins [ 29 , 30 ]. The current data do not allow to distinguish unambiguously, to what extent these phenotypes are caused by the absence of active Gv in the affected organs, by remote action of Gv in other organs, or by disturbance of developmentally earlier processes.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the function of the fifth class of Gα proteins: regulation of ionic homeostasis as unifying hypothesis

Abu Obaid,

Ivandic,

Korsching

2024

Cell. Mol. Life Sci.

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Trimeric G proteins transduce signals from a superfamily of receptors and each G protein controls a wide range of cellular and systemic functions. Their highly conserved alpha subunits fall in five classes, four of which have been well investigated (Gs, Gi, G12, Gq). In contrast, the function of the fifth class, Gv is completely unknown, despite its broad occurrence and evolutionary ancient origin (older than metazoans). Here we show a dynamic presence of Gv mRNA in several organs during early development of zebrafish, including the hatching gland, the pronephros and several cartilage anlagen, employing in situ hybridisation. Next, we generated a Gv frameshift mutation in zebrafish and observed distinct phenotypes such as reduced oviposition, premature hatching and craniofacial abnormalities in bone and cartilage of larval zebrafish. These phenotypes could suggest a disturbance in ionic homeostasis as a common denominator. Indeed, we find reduced levels of calcium, magnesium and potassium in the larvae and changes in expression levels of the sodium potassium pump atp1a1a.5 and the sodium/calcium exchanger ncx1b in larvae and in the adult kidney, a major osmoregulatory organ. Additionally, expression of sodium chloride cotransporter slc12a3 and the anion exchanger slc26a4 is altered in complementary ways in adult kidney. It appears that Gv may modulate ionic homeostasis in zebrafish during development and in adults. Our results constitute the first insight into the function of the fifth class of G alpha proteins.

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Genome wide detection of CNV and their association with body size in Danzhou chickens

Xie,

Shi,

Hou

et al. 2024

Poultry Science

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GNAS locus: bone related diseases and mouse models

Cited by 3 publications

References 143 publications

Targeted silencing of GNAS in a human model of osteoprogenitor cells results in the deregulation of the osteogenic differentiation program

Targeted silencing of GNAS in a human model of osteoprogenitor cells results in the deregulation of the osteogenic differentiation program

Deciphering the function of the fifth class of Gα proteins: regulation of ionic homeostasis as unifying hypothesis

Genome wide detection of CNV and their association with body size in Danzhou chickens

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