• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.459-466
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• 2016

Adipogenic differentiation of mesenchymal stem cells (MSCs) is critical for metabolic homeostasis and nutrient signaling during development. However, limited information is available on the pivotal modulators of adipogenic differentiation of MSCs. Adaptor protein Lnk (Src homology 2B3 [SH2B3]), which belongs to a family of SH2-containing proteins, modulates the bioactivities of different stem cells, including hematopoietic stem cells and endothelial progenitor cells. In this study, we investigated whether an interaction between insulin-like growth factor-1 receptor (IGF-1R) and Lnk regulated IGF-1-induced adipogenic differentiation of MSCs. We found that wild-type MSCs showed greater adipogenic differentiation potential than $Lnk^{-/-}$ MSCs. An ex vivo adipogenic differentiation assay showed that $Lnk^{-/-}$ MSCs had decreased adipogenic differentiation potential compared with wild-type MSCs. Interestingly, we found that Lnk formed a complex with IGF-1R and that IGF-1 induced the dissociation of this complex. In addition, we observed that IGF-1-induced increase in the phosphorylation of Akt and mammalian target of rapamycin was triggered by the dissociation of the IGF-1R-Lnk complex. Expression levels of a pivotal transcription factor peroxisome proliferator-activated receptor gamma ($PPAR-{\gamma}$) and its adipogenic target genes (LPL and FABP4) significantly decreased in $Lnk^{-/-}$ MSCs. These results suggested that Lnk adaptor protein regulated the adipogenesis of MSCs through the $IGF-1/Akt/PPAR-{\gamma}$ pathway.

• Journal of radiological science and technology
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• v.37 no.2
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• pp.109-116
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• 2014

Many studies have suggested that in the era of Drug-Eluting Stents(DES) are one of the causes of In-Stent Restenosis(ISR) of Stent Fracture(SF). The present study sought to evaluate clinical characteristics of patients with stent fracture after successful DES implantation. The 4,701 patients were selected for analysis who underwent a follow-up coronary angiography irrespective of ischemic symptoms. The overall incidence of SF was 32 patients(male:female=19:13, Av. age $62.44{\pm}9.8$year, 0.68%). Fractures of Sirolimus-Eluting Stents(SES), Paclitaxel-Eluting Stents(PES), Biolimus A9-Eluting Stents(BES), Everolimus-Eluting Etents(EES), Endothelial Progenitor Cell Capture Stent(EPC) and Zotarolimus-Eluting Stents(ZES) are accounted for 19(59.4%), 9(28.1%), 2(6.3%), 1(3.1%), 1(3.1%) and 0(0%) respectively. SF developed in the left Anterior Dscending(LAD) artery in 16 patients(50%) and in complex(type B2, C) lesions in 25 patients(69.4%). Ten patients were treated with heterogenous DES, the rest being treated with either homogenous DES(3 patients), plain old balloon angioplasty(3 patients), or conservative medical treatment(17 patients). None of the patients with SF suffered from cardiac death during a follow-up period of $32.9{\pm}12.4$ months. The overall rate of DES fracture over up to 3.7 years of follow-up was 0.68% with higher incidence in SES than in PES. SF frequently occurred in the LAD artery and in complex lesions. Of the patients with SF, coronary intervention was performed only when the binary restenosis lesion was significant. During the follow-up, patients with SF have continued on combination antiplatelet therapy. There is a very low rate of major adverse cardiac events(post-detection of SF), especially cardiac death associated with SF.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.3
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• pp.197-205
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• 2007

Angiogenesis is a essential part for bone formation and bone fracture healing. Vascular endothelial growth factor (VEGF), one of the most important molecules among many angiogenic factors, is a specific mitogen for vascular endothelial cells. VEGF-mediated angiogenesis is required for bone formation and repair. However, the effect of VEGF on osteoblastic cells during osteogenesis is still controversial. In recent days, substantial progress have been made toward developing tissue-engineered alternatives to autologous bone grafting for maxillofacial bony defects. Periosteum has received considerable interest as a better source of adult stem cells. Periosteum has the advantage of easy harvest and contains various cell types and progenitor cells that are able to differentiate into a several mesenchymal lineages, including bone. Several studies have reported the bone formation potential of periosteal cells, however, the correlation between VEGF signaling and cultured human periosteal cell-derived osteogenesis has not been fully investigated yet. The purpose of this study was to examine the correlation between VEGF signaling and cultured human periosteal-derived cells osteogenesis. Periosteal tissues of $5\;{\times}\;20\;mm$ were obtained from mandible during surgical extraction of lower impacted third molar from 3 patients. Periosteal-derived cells were introduced into the cell culture and were subcultured once they reached confluence. After passage 3, the periosteal-derived cells were further cultured for 42 days in an osteogenic inductive culture medium containing dexamethasone, ascorbic acid, and ${\beta}-glycerophosphate$. We evaluated the alkaline phosphatase (ALP) activity, the expression of Runx2 and VEGF, alizarin red S staining, and the quantification of osteocalcin and VEGF secretion in the periosteal-derived cells. The ALP activity increased rapidly up to day 14, followed by decrease in activity to day 35. Runx2 was expressed strongly at day 7, followed by decreased expression at day 14, and its expression was not observed thereafter. Both VEGF 165 and VEGF 121 were expressed strongly at day 35 and 42 of culture, particularly during the later stages of differentiation. Alizarin red S-positive nodules were first observed on day 14 and then increased in number during the entire culture period. Osteocalcin and VEGF were first detected in the culture medium on day 14, and their levels increased thereafter in a time-dependent manner. These results suggest that VEGF secretion from cultured human periosteal-derived cells increases along with mineralization process of the extracellular matrix. The level of VEGF secretion from periosteal-derived cells might depend on the extent of osteoblastic differentiation.