Role of angiogenesis in bone repair

Saran, Uttara; Gemini-Piperni, Sara; Chatterjee, Suvro

doi:10.1016/j.abb.2014.07.006

Cited by 303 publications

(281 citation statements)

References 225 publications

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“…In addition, FGF2 may also increase angiogenesis at the site of injury. A close spatial and temporal relationship exists between FGF signaling in skeletal development and disease GENES & DEVELOPMENTangiogenesis and osteogenesis during bone repair and endochondral bone formation, and the connection between the two processes is essential for bone formation (Dirckx et al 2013;Saran et al 2014). Recent genetic studies indicate that FGF/FGFR signaling plays an essential role in both processes.…”

Section: Fgf and Bone Regenerationmentioning

confidence: 99%

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: Fgf and Bone Regenerationmentioning

confidence: 99%

Fibroblast growth factor signaling in skeletal development and disease

2015

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“…Notably, MCP-1 levels were markedly low in HOS exosomes compared with MSC exosomes. Angiogenesis also plays an important role in fracture healing [46]. CM contains high levels of angiogenic factors such as VEGF and IL-6 and enhances bone ingrowth and fracture healing by stimulating endothelial cells [47].…”

Section: /2mentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model

Furuta

Miyaki

Ishitobi

et al. 2016

Stem Cells Translational Medicine

362

382

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Paracrine signaling by bone-marrow-derived mesenchymal stem cells (MSCs) plays a major role in tissue repair. Although the production of regulatory cytokines by MSC transplantation is a critical modulator of tissue regeneration, we focused on exosomes, which are extracellular vesicles that contain proteins and nucleic acids, as a novel additional modulator of cell-to-cell communication and tissue regeneration. To address this, we used radiologic imaging, histological examination, and immunohistochemical analysis to evaluate the role of exosomes isolated from MSC-conditioned medium (CM) in the healing process in a femur fracture model of CD9 2/2 mice, a strain that is known to produce reduced levels of exosomes. We found that the bone union rate in CD9 2/2 mice was significantly lower than wild-type mice because of the retardation of callus formation. The retardation of fracture healing in CD9 2/2 mice was rescued by the injection of exosomes, but this was not the case after the injection of exosomes-free conditioned medium (CM-Exo). The levels of the bone repairrelated cytokines, monocyte chemotactic protein-1 (MCP-1), MCP-3, and stromal cell-derived factor-1 in exosomes were low compared with levels in CM and CM-Exo, suggesting that bone repair may be in part mediated by other exosome components, such as microRNAs. These results suggest that exosomes in CM facilitate the acceleration of fracture healing, and we conclude that exosomes are a novel factor of MSC paracrine signaling with an important role in the tissue repair process. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1620-1630 SIGNIFICANCEThis work focuses on exosomes, which are extracellular vesicles, as a novel additional modulator of cell-to-cell communication. This study evaluated the role of exosomes isolated from mesenchymal stem cell (MSC)-conditioned medium (MSC-CM) in the fracture-healing process of CD9 2/2 mice, a strain that is known to produce reduced levels of exosomes. Retardation of fracture healing in CD9 2/2 mice was rescued by the injection of MSC exosomes, but this was not the case after the injection of exosome-free CM. This study finds that MSC exosomes are a novel factor of MSC paracrine signaling, with an important role in the tissue repair process.

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“…Indeed, failure of rapid revascularization will impair the tissue regeneration process. Not only there will be a lack of oxygen and nutrients supply, but the circulation of cells required for bone tissue formation will be hampered as well [2][3][4] . To stimulate revascularization, researchers have explored the addition of exogenous angiogenic growth factors, like vascular endothelial growth factor (VEGF), into the bone defect site 5,6) .…”

Section: Introductionmentioning

confidence: 99%

Characterization and angiogenic potential of xenogeneic bone grafting materials: Role of periodontal ligament cells

Rombouts

Jeanneau

Camilleri

et al. 2016

Dental Materials Journal

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Adequate revascularization is a prerequisite for successful healing of periodontal bone defects. This study characterized three different xenogeneic bone grafting materials: Gen-Os of equine and porcine origins, and anorganic Bio-Oss. We also investigated their angiogenic potential. All materials were composed of poorly crystalline calcium oxide phosphate, with Bio-Oss exhibiting a carbonated phase and larger particle size and both Gen-Os showing the presence of collagen. Both Gen-Os materials significantly enhanced vascular endothelial growth factor (VEGF) secretion by PDL cells. A significant increase in endothelial cell proliferation was observed in cultures with both Gen-Os conditioned media, but not with that of Bio-Oss. Finally, angiogenesis was stimulated by both Gen-Os conditioned media as demonstrated by an increased formation of capillary-like structures. Taken together, these findings indicate an enhanced angiogenic potential of both Gen-Os bone grafting materials when applied on PDL cells, most likely by increasing VEGF production.

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Role of angiogenesis in bone repair

Cited by 303 publications

References 225 publications

Fibroblast growth factor signaling in skeletal development and disease

Fibroblast growth factor signaling in skeletal development and disease

Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model

Characterization and angiogenic potential of xenogeneic bone grafting materials: Role of periodontal ligament cells

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