Trpv5/6 is vital for epithelial calcium uptake and bone formation

Vanoevelen, Jo; Janssens, Annelies; Huitema, Leonie F. A.; Hammond, Chrissy L.; Metz, Juriaan R.; Flik, G.; Voets, Thomas; Schulte‐Merker, Stefan

doi:10.1096/fj.11-183145

Cited by 61 publications

(71 citation statements)

References 60 publications

(70 reference statements)

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“…The mus mutant fish had impaired Ca 2 þ influx and significantly lower body Ca 2 þ content. 8 When exposed to low [Ca 2 þ ], all mus mutant larvae died, while their siblings remained viable. 8 Under normal [Ca 2 þ ], the mus mutant larvae had a dramatic increase in NaR cell number and pAkt-positive cells compared with their siblings (Figures 5a-d).…”

Section: Resultsmentioning

confidence: 98%

“…8 When exposed to low [Ca 2 þ ], all mus mutant larvae died, while their siblings remained viable. 8 Under normal [Ca 2 þ ], the mus mutant larvae had a dramatic increase in NaR cell number and pAkt-positive cells compared with their siblings (Figures 5a-d). The increases in Akt signaling and NaR cells are IGF1R-dependent (Figure 5e).…”

Section: Resultsmentioning

confidence: 98%

“…First, mus mutant larvae, which have a loss-of-function mutation in the trpv5/6 gene, 8 showed a dramatic increase in pAkt levels and elevated NaR cell proliferation rates under normal [Ca 2 þ ]. The elevated Akt signaling and NaR cell proliferation in the mus mutant larvae is IGF1R-dependent.…”

Section: Discussionmentioning

confidence: 99%

“…Zebrafish trpv5/6 mutant embryos were generated by crossing two identified adult fish heterozygous for the mus t25927 mutation. 8 Stained fish were genotyped following the published KASPar SNP genotyping method. 8 Whole-mount in situ hybridization.…”

Section: Discussionmentioning

confidence: 99%

“…10 In contrast to the presence of a separate TRPV5 gene and a TRPV6 gene in humans and mammals, zebrafish have a single trpv5/6 gene, thus eliminating concerns for possible functional redundancy and compensatory mechanisms seen in mammals. 8,11 In the adult stage, zebrafish trpv5/6 mRNA is expressed in the gills and intestine. 11 In the embryonic and larval stages, trpv5/6 is specifically expressed in NaR cells located on the surface of the yolk sac skin.…”

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confidence: 99%

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Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

et al. 2013

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Calcium deficiency causes abnormal colonic growth and increases colon cancer risk with poorly understood mechanisms. Here we elucidate a novel signaling mechanism underlying the Ca 2 þ deficiency-induced epithelial proliferation using a unique animal model. The zebrafish larval yolk sac skin contains a group of Ca 2 þ -transporting epithelial cells known as ionocytes. Their number and density increases dramatically when acclimated to low [Ca 2 þ ] environments. BrdU pulse-labeling experiments suggest that low [Ca 2 þ ] stimulates pre-existing ionocytes to re-enter the cell cycle. Low [Ca 2 þ ] treatment results in a robust and sustained activation of IGF1R-PI3K-Akt signaling in these cells exclusively. These ionocytes specifically express Igfbp5a, a high-affinity and specific binding protein for insulin-like growth factors (IGFs) and the Ca 2 þ -selective channel Trpv5/6. Inhibition or knockdown of Igfbp5a, IGF1 receptor, PI3K, and Akt attenuates low [Ca 2 þ ]-induced ionocyte proliferation. The role of Trpv5/6 was investigated using a genetic mutant, targeted knockdown, and pharmacological inhibition. Loss-of-Trpv5/6 function or expression results in elevated pAkt levels and increased ionocyte proliferation under normal [Ca 2 þ ]. These increases are eliminated in the presence of an IGF1R inhibitor, suggesting that Trpv5/6 represses IGF1R-PI3K-Akt signaling under normal [Ca 2 þ ]. Intriguingly, blockade of Trpv5/6 activity inhibits the low [Ca 2 þ ]-induced activation of Akt. Mechanistic analyses reveal that the low [Ca 2 þ ]-induced IGF signaling is mediated through Trpv5/6-associated membrane depolarization. Low extracellular [Ca 2 þ ] results in a similar amplification of IGF-induced PI3K-PDK1-Akt signaling in human colon cancer cells in a TRPV6-dependent manner. These results uncover a novel and evolutionarily conserved signaling mechanism that contributes to the abnormal epithelial proliferation associated with Ca 2 þ deficiency.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

et al. 2013

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Adaptive Materials Based on Iron Oxide Nanoparticles for Bone Regeneration

et al. 2018

ChemPhysChem

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The paper provides a brief overview of the use of iron oxide nanoparticles (IONPs) in the areas of bone regenerative medicine. Reconstruction of bone defects caused by trauma, non-union, and bone tumor excision, still faces many challenges despite the intense investigations and advancement in bone-tissue engineering and bone regeneration over the past decades. IONPs have promising prospects in this field due to their controlled responsive characteristics in specific external magnetic fields and have been of great interest during the last few years. This Minireview aims to summarize the relevant progress and describes the following five aspects: (i) The general introduction of IONPs, with a focus on the magnetic properties as the base of application; (ii) using IONPs as tools to study and control stem cells for better treatment efficacy in stem-cell-based bone defect repair; (iii) the use of IONPs and their complexes in the delivery of therapeutic agents, including chemical drug molecules, growth factors, and genetic materials, to promote osteogenesis-related cell function and differentiation, healthy bone tissue growth, and functional reconstruction; (iv) magneto-mechanical actuation in the regulation of cells distribution, mechano-transduction membrane receptors activation, and mechanosensitive signaling pathways regulation, and (v) fabrication, characteristics, and in vitro and in vivo osteogenic effects of magnetic composite bone scaffolds. Ongoing prospects are also discussed.

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Mechanisms of otoconia and otolith development

Lundberg

Thiessen

et al. 2014

Developmental Dynamics

128

134

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Otoconia are bio-crystals which couple mechanic forces to the sensory hair cells in the utricle and saccule, a process essential for us to sense linear acceleration and gravity for the purpose of maintaining bodily balance. In fish, structurally similar bio-crystals called otoliths mediate both balance and hearing. Otoconia abnormalities are common and can cause vertigo and imbalance in humans. However, the molecular etiology of these illnesses is unknown, as investigators have only begun to identify genes important for otoconia formation in recent years. To date, in-depth studies of selected mouse otoconial proteins have been performed, and about 75 zebrafish genes have been identified to be important for otolith development. This review will summarize recent findings as well as compare otoconia and otolith development. It will provide an updated brief review of otoconial proteins along with an overview of the cells and cellular processes involved. While continued efforts are needed to thoroughly understand the molecular mechanisms underlying otoconia and otolith development, it is clear that the process involves a series of temporally and spatially specific events that are tightly coordinated by numerous proteins. Such knowledge will serve as the foundation to uncover the molecular causes of human otoconia-related disorders.

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Trpv5/6 is vital for epithelial calcium uptake and bone formation

Cited by 61 publications

References 60 publications

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

Adaptive Materials Based on Iron Oxide Nanoparticles for Bone Regeneration

Mechanisms of otoconia and otolith development

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