Low dose fibroblast growth factor-2 (FGF-2) enhances bone morphogenetic protein-2 (BMP-2)-induced ectopic bone formation in mice

Nakamura, Yukio; Tensho, Keiji; Nakaya, Hiroyuki; Nawata, Masashi; Okabe, Takahiro; Wakitani, Shigeyuki

doi:10.1016/j.bone.2004.11.010

Cited by 106 publications

(99 citation statements)

References 20 publications

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“…Consistently, BMP2 expression is reduced in bones of Fgf2-null mice (Naganawa et al 2008). In line with this concept, BMP2 and FGF2 have a synergistic stimulatory effect on osteogenic function in human bone cells and in mice (Nakamura et al 2005;Kuhn et al 2013). Mechanistically, FGF2 enhances canonical BMP2 signaling in osteoblasts through promoting nuclear localization of RUNX2 and phospho-SMAD1/5/8 ).…”

Section: Intramembranous Mesenchymal Condensationsmentioning

confidence: 57%

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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Section: Intramembranous Mesenchymal Condensationsmentioning

confidence: 57%

Fibroblast growth factor signaling in skeletal development and disease

2015

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“…24 (1): [7][8][9][10][11][12][13][14][15][16], 2015 categorized as BMPs in humans. Among these, eight BMPs (BMP-1 to BMP-8a) have an osteochondral function 8) through phosphorylation of specific Smad proteins in mesenchymal stem cells 9,10) .…”

Section: Introductionmentioning

confidence: 99%

Combined Administration of BMP-2 and HGF Facilitate Bone Regeneration through Angiogenic Mechanisms

Masuda

Otsu

Kumakami-Sakano

et al. 2015

J. Hard Tissue Biology.

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Promotion of bone repair contributes to the shortening of the treatment period and improvement of the therapeutic effect in large bone defects. The purpose of the present study was to determine the optimal condition for the administration of growth factors to facilitate bone repair and explore the significance of angiogenesis in bone regeneration in vivo. Critical-size calvarial defects were created in the parietal bones of adult ddY mice, and the defects were treated with gelatin sponges impregnated with growth factors BMP-2, FGF-2, and HGF, alone or in combination. The bone regeneration at 1, 2, 3, and 4 weeks was evaluated using micro-computed tomography and histological observation. Critical-size calvarial defects were also created in Flk1-GFP mice to analyze angiogenesis in the early phase of bone repair. The proliferation of Flk1-GFP positive endothelial cells during bone repair was quantitatively evaluated using immunohistochemistry for Ki67. Treatment with a combination of BMP-2 and HGF (BMP-2+HGF) significantly induced more new bone formation within the bone defects compared with the other groups. Compared with BMP-2 alone, bone regeneration was rapidly increased by BMP-2+HGF from 3 weeks of the beginning of the treatment. The number of FLK1-GFP and Ki67 double positive cells in the defect areas of mice administered BMP-2+HGF at 1 week was larger than that in those administered BMP-2 alone. These results indicate that the combination of BMP-2 and HGF was markedly efficient in bone regeneration due to the promotion of angiogenesis in the early phase of bone repair.

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“…There are several candidates for increasing local bone formation: parathyroid hormone (PTH) 5, 6, anti‐sclerostin antibody 7, transforming growth factor (TGF)‐β1 8, fibroblast growth factor (FGF)‐2 9, FGF‐4 10, and various peptide drugs 11, 12, 13, 14, 15. Among these agents, small peptide drugs, which have a molecular weight of approximately 1,000–1,500, have many advantages because of their properties, which include their low production cost, non‐immunogenic properties, and facile modulation characteristics that allow for structural changes to be made to fit a drug target 11.…”

Section: Introductionmentioning

confidence: 99%

Peptide drugs accelerate BMP‐2‐induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling

et al. 2016

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Both W9 and OP3‐4 were known to bind the receptor activator of NF‐κB ligand (RANKL), inhibiting osteoclastogenesis. Recently, both peptides were shown to stimulate osteoblast differentiation; however, the mechanism underlying the activity of these peptides remains to be clarified. A primary osteoblast culture showed that rapamycin, an mTORC1 inhibitor, which was recently demonstrated to be an important serine/threonine kinase for bone formation, inhibited the peptide‐induced alkaline phosphatase activity. Furthermore, both peptides promoted the phosphorylation of Akt and S6K1, an upstream molecule of mTORC1 and the effector molecule of mTORC1, respectively. In the in vivo calvarial defect model, W9 and OP3‐4 accelerated BMP‐2‐induced bone formation to a similar extent, which was confirmed by histomorphometric analyses using fluorescence images of undecalcified sections. Our data suggest that these RANKL‐binding peptides could stimulate the mTORC1 activity, which might play a role in the acceleration of BMP‐2‐induced bone regeneration by the RANKL‐binding peptides.

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Low dose fibroblast growth factor-2 (FGF-2) enhances bone morphogenetic protein-2 (BMP-2)-induced ectopic bone formation in mice

Cited by 106 publications

References 20 publications

Fibroblast growth factor signaling in skeletal development and disease

Fibroblast growth factor signaling in skeletal development and disease

Combined Administration of BMP-2 and HGF Facilitate Bone Regeneration through Angiogenic Mechanisms

Peptide drugs accelerate BMP‐2‐induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling

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