Fibroblast Growth Factor 2 Induced Proliferation in Osteoblasts and Bone Marrow Stromal Cells: A Whole Cell Model

ObjectivesThe aim of this study was to examine the effect of basic fibroblast growth factor (FGF‐2) on osseointegration of dental implants with low primary stability in a beagle dog model.Materials and methodsCustomized titanium implants that were designed to have low contact with the existing bone were installed into the edentulous mandible of beagle dogs. To degrade the primary stability of the implants, the diameters of the bone sockets exceeded the implant diameters. FGF‐2 (0.3%) plus vehicle (hydroxypropyl cellulose) or vehicle alone was topically applied to the sockets in the FGF‐2 and control groups, respectively. In Study 1, the new bone area and length of new bone‐to‐implant contact (BIC) were evaluated at 4, 8, and 12 weeks after installation using histomorphometry and scanning electron microscopy. In Study 2, the implant stability quotient (ISQ) values were sequentially measured for 16 weeks using an Osstell system.ResultsThe histomorphometric analysis revealed that the new bone area and length of BIC in the FGF‐2 group were significantly larger than those in the control group at 4 weeks. Electron microscopic observation showed intimate contact between the mature lamellar bone and the implant surfaces, osseointegration, in both groups. The ISQ values in the FGF‐2 group were significantly increased from 6 to 16 weeks compared with those in the control group.ConclusionsTaken together, our study demonstrates that FGF‐2 promoted new bone formation around the dental implants and subsequent osseointegration, resulting in promotion of stability of implants with low primary stability.

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“…; Dupree et al. ) as well as endothelial cells (Gospodarowicz et al. ), fibroblasts, and osteoblasts (Rodan et al.…”

Section: Discussionmentioning

confidence: 99%

FGF‐2 promotes initial osseointegration and enhances stability of implants with low primary stability

Nagayasu-Tanaka

Nozaki

Miki

et al. 2016

Clinical Oral Implants Res

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“…More specifically, FGF2 has been shown to induce formation of new bone spicules within bone marrow devoid of bone (6). It is a pluripotent and pleiotropic member of a family of polypeptides that controls the proliferation and differentiation of various cell types, and plays a major role in tissue development, repair, and regeneration (7). In vitro, FGF2 has been shown to induce proliferation of osteoblasts and bone marrow stromal cells and to stimulate osteogenesis in bone marrow cells obtained from both young and adult intact rats and from early adolescent ovariectomized (OVX) rats (8).…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo evidence for stimulation of bone resorption by an EP4 receptor agonist and basic fibroblast growth factor: Implications for their efficacy as bone anabolic agents

Downey

Holliday

Aguirre

et al. 2009

Bone

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Prostaglandin E2 receptor subtype 4 agonists (EP4A) and basic fibroblast growth factor (FGF2) stimulate bone formation, but their effects on bone resorption are controversial. To provide additional insight into the skeletal effects of EP4A and FGF2, their regulation of expression of genes associated with bone formation and resorption in aged ovariectomized (OVX) rats and in cultured mouse bone marrow cells was determined. RNA was isolated from lumbar vertebrae of OVX rats (16 months of age) treated daily for 3 weeks with FGF2 or EP4A and processed for quantitative real time-PCR analyses. mRNA expression for the receptor activator of NF-κB ligand (RANKL) and cathepsin K (CTSK), but not osteoprotegerin (OPG), were upregulated by both FGF2 and EP4A. Addition of FGF2 and EP4A to the medium of cultured mouse bone marrow cells increased the formation of tartrate resistant acid phosphatase (TRAP) positive cells, upregulated the expression of RANKL and CTSK, and downregulated expression for OPG. EP4A also increased the formation of actin rings, an indicator of osteoclast activation, in a dose dependent manner in osteoclasts cultured on bone slices and triggered the formation of pits as revealed by a pitting assay. Gene expression for osterix (OSX) and IGF-2, genes associated with bone formation, was significantly greater in FGF2-treated OVX rats compared with EP4A-treated OVX rats. These findings at the molecular level are consistent with previous tissue-level histomorphometric findings, and at the doses tested, support the contention that FGF2 has a stronger bone anabolic effect than EP4A. The results of these in vivo and in vitro analyses clarify the effects of FGF2 and EP4A on bone formation and resorption, and provide insight into differences in the efficacy of two potential bone anabolic agents for restoration of lost bone mass in the osteopenic, estrogen-deplete skeleton.

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“…FGF2 has been well established as a potent mitogen for many cell types of mesodermal origin [73], and not surprisingly, it has likewise been shown to accelerate the proliferation rate of MSCs [74], thus allowing researchers to more readily obtain a sufficient number of cells for subsequent differentiation. Further, FGF2 has been shown to preserve the stemness and extend the lifespan of MSCs, allowing them to maintain their differentiation potential into later passages [75, 76].…”

Section: Stem Cell Regulation During Expansion Culturementioning

confidence: 99%

Stem Cell-based Tissue Engineering Approaches for Musculoskeletal Regeneration

Brown¹,

Handorf²,

Jeon³

et al. 2013

CPD

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The field of regenerative medicine and tissue engineering is an ever evolving field that holds promise in treating numerous musculoskeletal diseases and injuries. An important impetus in the development of the field was the discovery and implementation of stem cells. The utilization of mesenchymal stem cells, and later embryonic and induced pluripotent stem cells, opens new arenas for tissue engineering and presents the potential of developing stem cell-based therapies for disease treatment. Multipotent and pluripotent stem cells can produce various lineage tissues, and allow for derivation of a tissue that may be comprised of multiple cell types. As the field grows, the combination of biomaterial scaffolds and bioreactors provides methods to create an environment for stem cells that better represent their microenvironment for new tissue formation. As technologies for the fabrication of biomaterial scaffolds advance, the ability of scaffolds to modulate stem cell behavior advances as well. The composition of scaffolds could be of natural or synthetic materials and could be tailored to enhance cell self-renewal and/or direct cell fates. In addition to biomaterial scaffolds, studies of tissue development and cellular microenvironments have determined other factors, such as growth factors and oxygen tension, that are crucial to the regulation of stem cell activity. The overarching goal of stem cell-based tissue engineering research is to precisely control differentiation of stem cells in culture. In this article, we review current developments in tissue engineering, focusing on several stem cell sources, induction factors including growth factors, oxygen tension, biomaterials, and mechanical stimulation, and the internal and external regulatory mechanisms that govern proliferation and differentiation.

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Fibroblast Growth Factor 2 Induced Proliferation in Osteoblasts and Bone Marrow Stromal Cells: A Whole Cell Model

Cited by 29 publications

References 112 publications

FGF‐2 promotes initial osseointegration and enhances stability of implants with low primary stability

FGF‐2 promotes initial osseointegration and enhances stability of implants with low primary stability

In vitro and in vivo evidence for stimulation of bone resorption by an EP4 receptor agonist and basic fibroblast growth factor: Implications for their efficacy as bone anabolic agents

Stem Cell-based Tissue Engineering Approaches for Musculoskeletal Regeneration

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