In Vitro Osteoblast Differentiation is Negatively Regulated by Hoxc8

Zheng, Yanjun; Chung, Hyun Kee; Min, Hyehyun; Kang, Myengmo; Kim, Seong Hwan; Gadi, Jogeswar; Kim, Myoung Hee

doi:10.1007/s12010-009-8558-3

Cited by 9 publications

(9 citation statements)

References 17 publications

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“…miR‐196 family members play important roles in the proliferation and osteogenic differentiation of cells (Kim et al., ). Previous studies have shown that overexpression of miR‐196a could enhance osteogenic differentiation, and promote the commitment of mesenchymal stem cells to the osteoblast lineage through targeting HOXC8 (MIM# 142970) gene, which is essential for osteoblast differentiation (Kim et al., ; Zheng et al., ). In this study, FGF2 was experimentally validated as an in vitro target, which suggests a potential regulation mechanism by which hsa‐miR196a‐3p was involved in osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

A functional SNP regulated by miR-196a-3p in the 3′UTR ofFGF2is associated with bone mineral density in the Chinese population

et al. 2017

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Previous studies have identified FGF2 as a susceptibility gene for osteoporosis in Caucasians. Evaluating the genetic associations in different ethnicities is necessary. Moreover, elucidating the functional mechanism for the susceptibility loci is important to offer new targets for therapeutic studies. Here, we genotyped 10 SNPs in FGF2 and tested for associations with bone mineral density (BMD) in a discovery sample of 1,300 Chinese subjects. Nominally significant results were subjected to replication in another sample of 1,039 Chinese subjects. We identified one SNP rs1048201:C>T in FGF2 3'untranslated region significantly associated with spine BMD (combined cohorts, P = 1.53×10 ). Expression quantitative trait locus analyses revealed that rs1048201 also affected FGF2 gene expression (P = 7.03×10 ). Bioinformatics prediction suggested that rs1048201 T allele could disrupt miRNA binding. Luciferase assay validated that the C allele had a repressive effect on FGF2 gene expression. We found that hsa-miR-196a-3p affected expression on both mRNA and protein levels of FGF2. In conclusion, our study provided evidence that a functional SNP rs1048201 was associated with BMD, and SNP rs1048201:C>T variant may act by affecting binding of hsa-miR-196a-3p. The SNP-modified posttranscriptional gene regulation by miRNA could be a potentially pathogenetic mechanism of osteoporosis.

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Section: Discussionmentioning

confidence: 99%

A functional SNP regulated by miR-196a-3p in the 3′UTR ofFGF2is associated with bone mineral density in the Chinese population

et al. 2017

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“…By regulating the Hox genes (Hoxb8, Hoxc8, Hoxd8, Hoxa7), miR-196 family members play a crucial role in development of the axial skeleton, fine-tuning levels of HOX proteins in a temporal and spacial manner [70-76]. miR-196a promotes commitment of mesenchymal stem cells (MSCs) towards the osteoblast lineage by targeting Hoxc8 [77, 78].…”

Section: Mir-snps: Snps In Mirna Genes Altering Their Biogenesis Amentioning

confidence: 99%

“…miR-196a promotes commitment of mesenchymal stem cells (MSCs) towards the osteoblast lineage by targeting Hoxc8 [77, 78]. In osteoblasts, Hoxc8 acts as a negative regulator of differentiation and transcriptionally suppresses osteopontin [72, 73, 76]. In turn, BMP signaling represses Hoxc8 activity through SMAD1 interaction with Hoxc8, relieving repression of osteopontin transcription.…”

Section: Mir-snps: Snps In Mirna Genes Altering Their Biogenesis Amentioning

confidence: 99%

MicroRNA variants as genetic determinants of bone mass

Dole

Delany

2016

Bone

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Single nucleotide polymorphisms (SNPs) are the most abundant genetic variants that contribute to the heritability of bone mass. MicroRNAs (miRNAs, miRs) are key post-transcriptional regulators that modulate the differentiation and function of skeletal cells by targeting multiple genes in same or distinct signaling pathways. SNPs in miRNA genes and miRNA binding sites can alter miRNA abundance and mRNA targeting. This review describes the potential impact of miRNA-related SNPs on skeletal phenotype. Although many associations between SNPs and bone mass have been described, this review is limited to gene variants for which a function has been experimentally validated. SNPs in miRNA genes (miR-SNPs) that impair miRNA processing and alter the abundance of mature miRNA are discussed for miR-146a, miR-125a, miR-196a, miR-149 and miR-27a. SNPs in miRNA targeting sites (miR-TS-SNPs) that alter miRNA binding are described for the bone remodeling genes bone morphogenetic protein receptor 1 (Bmpr1), fibroblast growth factor 2 (Fgf2), osteonectin (Sparc) and histone deacetylase 5 (Hdac5). The review highlights two aspects of miRNA-associated SNPs: the mechanism for altering miRNA mediated gene regulation, and the potential of miR-associated SNPs to alter osteoblast, osteoclast or chondrocyte differentiation and function. Given the polygenic nature of skeletal diseases like osteoporosis and osteoarthritis, validating the function of additional miRNA-associated SNPs has the potential to enhance our understanding of the genetic determinants of bone mass and predisposition to selected skeletal diseases.

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“…In many studies, enamel matrix derivative enhanced the proliferation of osteoprogenitors , whilst numerous studies found that their differentiation (estimated by measuring alkaline phosphatase activity, expression of alkaline phosphatase, osteocalcin or core‐binding factor alpha‐1 or biomineralization) was invariably stimulated by enamel matrix derivative . Obviously, these cells were used to test the possible stimulatory effects of other biomolecules, such as bone morphogenetic protein‐2 and bone morphogenetic protein‐7 .…”

Section: In Vitro Models Of Periodontal Regenerationmentioning

confidence: 99%

In vitro models for evaluation of periodontal wound healing/regeneration

Weinreb¹,

Nemcovsky²

2015

Periodontology 2000

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Periodontal wound healing and regeneration are highly complex processes, involving cells, matrices, molecules and genes that must be properly choreographed and orchestrated. As we attempt to understand and influence these clinical entities, we need experimental models to mimic the various aspects of human wound healing and regeneration. In vivo animal models that simulate clinical situations of humans can be costly and cumbersome. In vitro models have been devised to dissect wound healing/regeneration processes into discrete, analyzable steps. For soft tissue (e.g. gingival) healing, in vitro models range from simple culture of cells grown in monolayers and exposed to biological modulators or physical effectors and materials, to models in which cells are 'injured' by scraping and subsequently the 'wound' is filled with new or migrating cells, to three-dimensional models of epithelial-mesenchymal recombination or tissue explants. The cells employed are gingival keratinocytes, fibroblasts or endothelial cells, and their proliferation, migration, attachment, differentiation, survival, gene expression, matrix production or capillary formation are measured. Studies of periodontal regeneration also include periodontal ligament fibroblasts or progenitors, osteoblasts or osteoprogenitors, and cementoblasts. Regeneration models measure cellular proliferation, attachment and migration, as well as gene expression, transfer and differentiation into a mineralizing phenotype and biomineralization. Only by integrating data from models on all levels (i.e. a single cell to the whole organism) can various critical aspects of periodontal wound healing/regeneration be fully evaluated.

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In Vitro Osteoblast Differentiation is Negatively Regulated by Hoxc8

Cited by 9 publications

References 17 publications

A functional SNP regulated by miR-196a-3p in the 3′UTR ofFGF2is associated with bone mineral density in the Chinese population

A functional SNP regulated by miR-196a-3p in the 3′UTR ofFGF2is associated with bone mineral density in the Chinese population

MicroRNA variants as genetic determinants of bone mass

In vitro models for evaluation of periodontal wound healing/regeneration

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