• Development and Reproduction
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• v.27 no.3
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• pp.137-147
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• 2023

Pharyngeal pouches are an important epithelial structure controlling facial skeletal development in vertebrates. A series of pouches arise sequentially in the pharyngeal endoderm through collective cell migration followed by rearrangement of pouch-forming cells. While crucial transcription factors and signaling molecules have been identified in pouch formation, a role for Neuropilins (Nrps) in pouch development has not yet been analyzed in any vertebrates. Nrps are cell surface receptors essential for angiogenesis and axon guidance. In all vertebrates, the two Nrp family members, Nrp1 and Nrp2, are conserved in the genome, with two paralogs for Nrp1 (Nrp1a and Nrp1b) and Nrp2 (Nrp2a and Nrp2b) being identified in zebrafish. Here, I report a potential requirement of Nrp signaling in pouch development in zebrafish. nrp1a and nrp2b were expressed in the developing pouches, with sema3d, a ligand for Nrps, being expressed in the pouches. Knocking down Nrps signaling in the pharyngeal endoderm led to severe defects in pouches and facial cartilages. In addition, blocking Mitogen-activated protein kinase (MAPK) activities, a downstream effector of Nrp signaling, in the pharyngeal endoderm caused similar defects in pouches and facial skeleton to those by knocking down Nrps signaling. My results suggest that Nrp signaling acts for pouch formation through MAPK.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.3
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• pp.217-224
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• 2008

Angiogenesis plays an important role in bone development and postnatal bone fracture repair. Vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFRs) have been thought to be primarily involved in promoting angiogenesis. It is well known that VEGF and its receptors have been reported to play an important role in the regulation of the interaction between angiogenesis and osteogenesis during bone repair processes. Dexamethasone, a potent synthetic glucocorticoid, promotes phenotype markers of osteoblast differentiation, such as ALP and osteocalcin. It stimulates in vitro osteogenesis of human bone marrow osteogenic stromal cells. Dexamethasone has been reported to suppress VEGF gene expression in some cells. However, our previous study demonstrated VEGF quantification increased in a time-dependent manner in periosteal-derived osteogenesis under dexamethasone. So, the purpose of this study was to examine the angiogenic phenotypes in cultured human periosteal-derived cells under high-dose dexamethasone. Periosteal-derived cells were cultured using a technique previously described. After passage 3, the periosteal-derived cells were further cultured for 28 days in an osteogenic inductive culture medium containing ascorbic acid, ${\beta}$-glycerophosphate and high-dose dexamethasone, We evaluated the expression of VEGF isoforms, VEGFR-1, VEGFR-2, and neuropilin-1, ALL VEGF isoforms ($VEGF_{121},\;VEGF_{165},\;VEGF_{189}$, and $VEGF_{206}$) expression was observed by RT-PCR analysis. VEGFR-1, VEGFR-2 and neuropilin-1 expression increased up to day 14, particularly during the early stage of mineralization. Our results suggest the involvement of direct VEGFs/VEGFRs system on periosteal-derived cells during early mineralization phase under high-dose of dexamethasone. These also suggest that VEGF might act as an autocrine growth molecule during osteoblastic differentiation of cultured human periosteal-derived cells.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.4
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• pp.205-212
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• 2009

Purpose : The purpose of this study was to examine the expression of various angiogenic factors during osteoblastic differentiation of periostealderived cells and the effects of osteogenic inductive medium of periosteal-derived cells on the proliferation of endothelial progenitor cells. Materials and methods : Periosteal-derived cells were obtained from mandibular periosteums and introduced into the cell culture. After passage 3, the cells were divided into two groups and cultured for 21 days. In one group, the cells were cultured in the DMEM supplemented with osteogenic inductive agent, including 50g/ml L-ascorbic acid 2-phosphate, 10 nM dexamethasone and 10 mM -glycerophosphate. In the other group, they were cultured in DMEM supplemented without osteogenic inductive agent. VEGF isoforms, VEGFR-1, VEGFR-2, and neuropilin-1 mRNA expression was observed. Human umbilical cord blood-derived endothelial progenitor cell proliferation was also observed. Results : The expression of VEGF isoforms was higher in osteogenic inductive medium than in non-osteogenic inductive medium. The expression of VEGFR-2 was also higher in osteogenic inductive medium than in non-osteogenic inductive medium. However, the expression of VEGFR-1 and neuropilin-1 was similar in both osteogenic inductive medium and non-osteogenic inductive medium. In addition, conditioned medium from differentiated periosteal-derived cells stimulated human umbilical cord blood-derived endothelial progenitor cell numbers compared to conditioned medium from non-differentiated periosteal-derived cells. Conclusion : These results suggest that in vitro osteoblastic differentiation of periosteal-derived cells has angiogenic capacity to support endothelial progenitor cell numbers.

• Journal of Korean Neurosurgical Society
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• v.50 no.4
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• pp.281-287
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• 2011

Objective : Pituitary apoplexy is life-threatening clinical syndrome caused by the rapid enlargement of a pituitary tumor due to hemorrhage and/or infarction. The pathogenesis of pituitary apoplexy is not completely understood. We analyzed the magnetic resonance imaging (MRI) of pituitary tumors and subsequently correlated the radiological findings with the clinical presentation. Additionally, immunohistochemistry was also performed to determine whether certain biomarkers are related to radiological apoplexy. Methods : Thirty-four cases of pituitary adenoma were enrolled for retrospective analysis. In this study, the radiological apoplexy was defined as cases where hemorrhage, infarction or cysts were identified on MRI. Acute clinical presentation was defined as the presence of any of the following symptoms: severe sudden onset headache, decreased visual acuity and/or visual field deficit, and acute mental status changes. Angiogenesis was quantified by immunohistochemical expression of fetal liver kinase 1 (Flk-1), neuropilin (NRP) and vascular endothelial growth factor (VEGF) expression, while microvascular density (MVD) was assessed using Endoglin and CD31. Results : Clinically, fourteen patients presented with acute symptoms and 20 for mild or none clinical symptoms. Radiologically, fifteen patients met the criteria for radiological apoplexy. Of the fifteen patients with radiologic apoplexy, 9 patients presented acute symptoms whereas of the 19 patient without radiologic apoplexy, 5 patients presented acute symptoms. Of the five biomarkers tracked, only VEGF was found to be positively correlated with both radiological and nonradiological apoplexy. Conclusion : While pituitary apoplexy is currently defined in cases where clinical symptoms can be histologically confirmed, we contend that cases of radiologically identified pituitary hemorrhages that present with mild or no symptoms should be designated subacute or subclinical apoplexy. VEGF is believed to have a positive correlation with pituitary hemorrhage. Considering the high rate of symptomatic or asymptomatic pituitary tumor hemorrhage, additional studies are needed to detect predictors of the pituitary hemorrhage.