High extracellular calcium-induced NFATc3 regulates the expression of receptor activator of NF-κB ligand in osteoblasts

Lee, Hye-Lim; Bae, O.-Y.; Baek, Kyung Hwa; Kwon, Ae‐Ran; Hwang, Hyo Rin; Qadir, Abdul; Park, Hyun-Jung; Woo, Kyung Mi; Ryoo, Hyun‐Mo; Baek, Jeong‐Hwa

doi:10.1016/j.bone.2011.04.006

Cited by 35 publications

(45 citation statements)

References 35 publications

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“…Additionally, heterozygous EDC4 knockout mice showed a change in bone density, though it was not significant (Origins of bone and cartilage disease project, 2015). NFATC3 regulates the expression of the NF-κB ligand receptor activator in osteoblasts and is therefore involved in osteoclastogenesis (Lee et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

Genome-wide QTL mapping results for regional DXA body composition and bone mineral density traits in pigs

Bernau¹,

Kremer-Rücker

Međugorac³

et al. 2017

Arch. Anim. Breed.

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Abstract. In a previous study, genome-wide mapping of quantitative trait loci (QTL) for five body composition traits, three bone mineral traits and live weight was performed using whole-body dual-energy X-ray absorptiometry (DXA) data. Since QTL for bone mineral traits were rare, the current study aimed to clarify whether the mapping results were influenced by the analysed body regions. Thus, the same material (551 pigs) and methods as in the whole-body QTL mapping study were used. However, for evaluation of the DXA scans, we manually defined two body regions: (i) from the last ribs to the pelvis (A) and (ii) including the pelvis and the hind limbs (P). Since live weight was not affected by the regional analysis, it was omitted from the QTL mapping design.Our results show an overall high consistency of mapping results especially for body composition traits. Two thirds of the initial whole-body QTL are significant for both A and P. Possible causes for the still low number of bone mineral QTL and the lower consistency found for these traits are discussed. For body composition traits, the data presented here show high genome-wide Pearson correlations between mapping results that are based on DXA scans with the time-saving "whole-body standard setting" and mapping results for DXA data that were obtained by time-consuming manual definition of the regions of interest. However, our results also suggest that whole-body or regional DXA scans might generally be less suitable for mapping of bone mineral traits in pigs. An analysis of single reference bones could be more useful.

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Section: Resultsmentioning

confidence: 99%

Genome-wide QTL mapping results for regional DXA body composition and bone mineral density traits in pigs

Bernau¹,

Kremer-Rücker

Međugorac³

et al. 2017

Arch. Anim. Breed.

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“…Nell-1 stimulates expression of extracellular matrix proteins that are required for bone and cartilage cell differentiation [83]. NFATc3 may play a role in bone homeostasis through responding to high extracellular calcium level and stimulating RANKL production in osteoblasts which in turn drives the activity of osteoclasts [84]. The roles of NFATc2, c3 and c4 in bone homeostasis are not well understood and further studies are needed.…”

Section: Roles Of Nfatc2 and Nfatc3 In Osteoblastsmentioning

confidence: 99%

NFAT Signaling and Bone Homeostasis

Chen¹,

Pan²

2013

J Hematol Thrombo Diseases

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Bone homeostasis is a function of the constant balancing acts between osteoclasts and osteoblasts, regulated by numerous factors in cellular and molecular levels. Calcineurin-NFAT pathway plays critical roles in bone homeostasis by regulating many aspects of bone development and remodeling. NFATc1 is the master transcription factor of osteoclasts, acting downstream of RANKL (receptor activator of nuclear factor-κB ligand) to control osteoclastogenesis. NFATc1 also plays important role in osteoblastogenesis, its increased nuclear occupancy in osteoblasts causes osteopetrosis by regulating chemokine and Wnt pathways. Targeting NFAT pathway may provide therapeutic avenues for treating bony disorders.

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“…A critical role of BMP-2-activated phosphatidylinositol 3-kinase and its downstream partner Akt kinase is established in BMP-2-induced osteoblast differentiation and CSF-1 expression and secretion from osteoblasts to support active osteoclast formation (15,25). NFATc1 regulates osteoclast differentiation by transcriptionally activating RANKL that feeds back to induce NFATc1 (7,12,26). Experimental evidence also suggests a role of NFATc1 in osteoblast-assisted osteoclast activity (13).…”

mentioning

confidence: 99%

“…One such partner is identified to be the osteoblastic transcription factor osterix (10). Of the five NFAT isoforms, expression in the mouse osteoblasts is limited to NFATc1 and NFATc3 where NFATc1 regulates NFATc3 expression (7). Calcineurin and NFATc1 control osteoblast proliferation and expression of tartrate-resistant acid phosphatase, the osteoclast-associated receptor cathepsin K, and calcitonin receptor to induce osteoclast differentiation (11)(12)(13).…”

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confidence: 99%

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Bone Morphogenetic Protein-2 (BMP-2) Activates NFATc1 Transcription Factor via an Autoregulatory Loop Involving Smad/Akt/Ca2+ Signaling

Mandal¹,

Das²,

Ganapathy³

et al. 2016

Journal of Biological Chemistry

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Background: Mutations in NFATc1 and BMP-2 genes result in bone abnormalities in mice. Results: BMP-2 activates intracellular Ca 2ϩ release, thus activating calcineurin phosphatase to induce NFATc1 expression involving canonical Smad and noncanonical PI 3-kinase in osteoblasts. Conclusion: BMP-2-stimulated Ca 2ϩ -calcineurin-NFATc1 axis potentiates osteoblast differentiation. Significance: NFATc1 autoregulates its expression in response to BMP-2 in osteoblasts.

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High extracellular calcium-induced NFATc3 regulates the expression of receptor activator of NF-κB ligand in osteoblasts

Cited by 35 publications

References 35 publications

Genome-wide QTL mapping results for regional DXA body composition and bone mineral density traits in pigs

Genome-wide QTL mapping results for regional DXA body composition and bone mineral density traits in pigs

NFAT Signaling and Bone Homeostasis

Bone Morphogenetic Protein-2 (BMP-2) Activates NFATc1 Transcription Factor via an Autoregulatory Loop Involving Smad/Akt/Ca2+ Signaling

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