Knockout of Nuclear High Molecular Weight FGF2 Isoforms in Mice Modulates Bone and Phosphate Homeostasis

Homer-Bouthiette, Collin; Doetschman, Thomas; Xiao, Liping; Hurley, Marja M.

doi:10.1074/jbc.m114.619569

Cited by 27 publications

(31 citation statements)

References 45 publications

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“…First, we establish the importance of HMW-FGF-2 regulation of the FGF-23 promoter activity in vitro and establish the involvement of the INFS pathway in regulating FGF-23 gene transcription. Our observations are consistent with the findings that transgenic overexpression of HMW-FGF-2, the ligand for nuclear FGFR1, stimulates FGF-23 expression in bone and that HMW-FGF-2 is increased in bone of adult Hyp mice (26), that the conditional deletion of FGFR1 in osteocytes reduces FGF-23 in the Hyp mouse models of increased FGF-23 (32), and the deletion of HMW-FGF-2 in mice reduces FGF-23 expression in vivo (48).…”

Section: Discussionsupporting

confidence: 78%

Membrane and Integrative Nuclear Fibroblastic Growth Factor Receptor (FGFR) Regulation of FGF-23

Han

Xiao

Quarles

2015

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 78%

Membrane and Integrative Nuclear Fibroblastic Growth Factor Receptor (FGFR) Regulation of FGF-23

Han

Xiao

Quarles

2015

Journal of Biological Chemistry

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“…High-molecular-weight FGF2 overexpression in osteoblast precursor cells results in the inhibition of osteoblast differentiation and matrix mineralization through FGF23/FGFR/MAPK signaling, independently of phosphate wasting . Conversely, genetic inactivation of the FGF2 high-molecular-weight isoforms caused increased bone mass due to increased osteoblast differentiation and decreased oscteoclast activity associated with decreased FGF23 expression, indicating a negative impact of high-molecularweight FGF2 isoforms on bone cell metabolism and phosphate homeostasis (Homer-Bouthiette et al 2014). These findings highlight the functional implications of distinct FGF2 isoforms on FGF23 secretion, bone cell activity, and bone matrix mineralization.…”

Section: Fgf/fgfr Signaling In Osteoblastogenesismentioning

confidence: 74%

Fibroblast growth factor signaling in skeletal development and disease

2015

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Fibroblast growth factor (FGF) signaling pathways are essential regulators of vertebrate skeletal development. FGF signaling regulates development of the limb bud and formation of the mesenchymal condensation and has key roles in regulating chondrogenesis, osteogenesis, and bone and mineral homeostasis. This review updates our review on FGFs in skeletal development published in Genes & Development in 2002, examines progress made on understanding the functions of the FGF signaling pathway during critical stages of skeletogenesis, and explores the mechanisms by which mutations in FGF signaling molecules cause skeletal malformations in humans. Links between FGF signaling pathways and other interacting pathways that are critical for skeletal development and could be exploited to treat genetic diseases and repair bone are also explored.

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“…In the osteoclast lineage, FGF2 promotes recruitment of osteoclast precursors and their differentiation [120, 121, 123]. FGF2-null mice display osteopenia and decreased bone remodeling [124, 125]. …”

Section: Mir-ts-snps Implicated In Skeletal Diseasementioning

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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Knockout of Nuclear High Molecular Weight FGF2 Isoforms in Mice Modulates Bone and Phosphate Homeostasis

Cited by 27 publications

References 45 publications

Membrane and Integrative Nuclear Fibroblastic Growth Factor Receptor (FGFR) Regulation of FGF-23

Membrane and Integrative Nuclear Fibroblastic Growth Factor Receptor (FGFR) Regulation of FGF-23

Fibroblast growth factor signaling in skeletal development and disease

MicroRNA variants as genetic determinants of bone mass

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