• Journal of Periodontal and Implant Science
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• 제34권1호
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• pp.177-193
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• 2004

Several experimental studies showed that the application of small amounts of electric current to bone stimulated osteogenesis at the site of the cathode and suggested that electrical currents promote osseointegration around dental implants. The purpose of this study was to determine the effect of direct microcurrent to endosseous titanium implants placed in bone defects. The right and left 2nd, 3rd and 4th mandibular premolars in ten mongrel dogs (15Kg of weight) were extracted. One monthe later, Ti-machined screw type implants(3.8 mm diameter x 8.5 mm length, $AVANA^{(R)}$, Ostem) were placed in surgically created circumferential defect area(width 5mm, depth 4mm). The implants were divided into three groups according to the treatment modalities: Control group- implants without electrical stimulation; Experimental group I- implants with allogenic demineralized freeze dried bone grafting; and Experimental group II-implants allogenic demineralized freeze dried bone grafting and electric stimulation. The animals were sacrificed in the 4th and 8th week after implant placement and un-decalcified specimens were prepared for histological and histometrical evaluation of bone-implant contact ratio (BIC) and bone formation area ratio (BFA) in defect area. Some specimens at 8 weeks after implantation were used for removal torque testing. Histologically, there was connective tissue infiltration in the coronal part of defect area in control and the experimental group I, whereas direct bone contact was found in the experimental group II without connective tissue invasion. Average BIC ratios at 4 weeks of healing were 60.1% in the experimental group II, 47.4% in the experimental group I and 42.7% in the control. Average BIC ratios at 8 weeks after implantation were 67.6% in the experimental group II, 55.9% in the experimental group I and 54.6% in the control. The average BFA ratio was 84.0% in the experimental group II, 71.8% in the experimental group I and 58.8% in the control at 4 weeks, and the BFA ratios were 89.6% in the experimental group II, 81.4% in the experimental group I and 70.5% in the control at 8 weeks after implantation. The experimental group II showed also significantly greater BIC and BFA ratios compared to the control and the experimental group I (p<0.05). The removal torque values at 8 weeks after implantation were 56 Ncm in the experimental group II, 49 Ncm in the experimental group I and 43 Ncm in the control. There was a statistically significant difference among 3 groups (p<0.05). These results suggest that electrical stimulation improve and accelerate bone healing around endosseous titanium implants in bone defect.

• Journal of Periodontal and Implant Science
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• 제44권5호
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• pp.242-250
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• 2014

Purpose: This study aimed to evaluate the effects of fibronectin and oxysterol immobilized on machined-surface dental implants for the enhancement of cell attachment and osteogenic differentiation, on peri-implant bone healing in the early healing phase using an experimental model in dogs. Methods: Five types of dental implants were installed at a healed alveolar ridge in five dogs: a machined-surface implant (MI), apatite-coated MI (AMI), fibronectin-loaded AMI (FAMI), oxysterol-loaded AMI (OAMI), and sand-blasted, large-grit, acid-etched surface implant (SLAI). A randomly selected unilateral ridge was observed for 2 weeks, and the contralateral ridge for a 4-week period. Histologic and histometric analyses were performed for the bone-to-implant contact proportion (BIC) and bone density around the dental implant surface. Results: Different bone healing patterns were observed according to the type of implant surface 2 weeks after installation; newly formed bone continuously lined the entire surfaces in specimens of the FAMI and SLAI groups, whereas bony trabecula from adjacent bone tissue appeared with minimal new bone lining onto the surface in the MI, AMI, and OAMI groups. Histometric results revealed a significant reduction in the BIC in MI, AMI, and OAMI compared to SLAI, but FAMI demonstrated a comparable BIC with SLAI. Although both the BIC and bone density increased from a 2- to 4-week healing period, bone density showed no significant difference among any of the experimental and control groups. Conclusions: A fibronectin-coated implant surface designed for cell adhesion could increase contact osteogenesis in the early bone healing phase, but an oxysterol-coated implant surface designed for osteoinductivity could not modify early bone healing around implants in normal bone physiology.

• Molecules and Cells
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• 제38권7호
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• pp.643-650
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• 2015

The use of conditioned medium from mesenchymal stem cells may be a feasible approach for regeneration of bone defects through secretion of various components of mesenchymal stem cells such as cytokines, chemokines, and growth factors. Mesenchymal stem cells secrete and accumulate multiple factors in conditioned medium under specific physiological conditions. In this study, we investigated whether the conditioned medium collected under hypoxic condition could effectively influence bone regeneration through enhanced migration and adhesion of endogenous mesenchymal stem cells. Cell migration and adhesion abilities were increased through overexpression of intercellular adhesion molecule-1 in hypoxic conditioned medium treated group. Intercellular adhesion molecule-1 was upregulated by microRNA-221 in mesenchymal stem cells because microRNAs are key regulators of various biological functions via gene expression. To investigate the effects in vivo, evaluation of bone regeneration by computed tomography and histological assays revealed that osteogenesis was enhanced in the hypoxic conditioned medium group relative to the other groups. These results suggest that behavioral changes of endogenous mesenchymal stem cells through microRNA-221 targeted-intercellular adhesion molecule-1 expression under hypoxic conditions may be a potential treatment for patients with bone defects.

• 대한소아치과학회지
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• 제27권2호
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• pp.300-308
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• 2000

Fibroblast growth factor(FGF)는 세포의 성장과 이동, 분화와 생존과 관련된 여러가지 과정을 조절하는 것으로 알려져 있다. 이들의 prototype인 FGF-1과 FGF-2는 FGF receptors (FGFRs)를 통해서 세포내로 신호를 전달하는데, 두개봉합부의 조기융합을 보이는 craniosynostosis는 FGFRs중, 특히 FGFR-2의 point mutation에 의해서 야기된다. 최근 여러 보고에서 FGF/FGFR 신호전달은 골아세포의 분화에 있어 필수적인 역할을 한다고 하였으며, bFGF soaked bead를 쥐 두개골의 시상봉합부의 mid-mesenchyme과 osteogenic front부위에 적용하였을 때 osteopontin(OPN) 유전자의 발현을 유도한다고 하였다. 이에 본 연구에서는 ST-2 cell line를 이용한 in vitro실험에서 bFGF가 OPN 유전자 발현에 미치는 영향과 그 기전을 Northern blot analysis를 통해서 연구하고자 하였다. 1 ng/ml bFGF의 투여는 OPN, fibronectin 유전자 발현을 증가시켰으며, type I collagen 유전자 발현은 감소시켰으나 alkaline phosphatase 유전자 발현에는 영향을 미치지 않았다. OPN은 그 발현양상이 bFGF의 농도 증가에 따라 증가하는 양상으로 나타났으며, 시간결과에 따른 발현양상도 bFGF 투여 3시간째부터 bFGF를 투여한 군에서 대조군에 비해 높게 나타났으며 이는 24시간까지 시간의 경과에 따라 증가하는 양상을 보였다. 단백질 합성 억제제인 cycloheximide를 처리한 군에서는 OPN의 증가 양상을 보이지 않았는데 이는 bFGF에 의한 OPN유전자 발현이 새로운 전사조절 단백질 합성 등의 여러 단계를 거쳐서 일어남을 의미한다. 결론적으로 bFGF는 새로운 전사조절 단백질의 합성을 통해서 OPN 유전자 발현을 농도 및 시간 의존적으로 증가시킨다.

• 한국방사선학회논문지
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• 제5권1호
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• pp.11-18
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• 2011

다능성 세포를 포함하는 골막은 골모세포와 연골세포로 분화될 수 있다. 그리고 배양된 골막유래세포는 골형성 능력을 가지고 있다. 이 연구의 목적은 골막유래 세포들과 골이식재 간의 상호작용을 평가하는 것이다. Sprague-Dawley 랫드의 두개골 골막에서 세포를 분리한 다음, 배양된 골막유래세포를 beta-tricalcium phosphate (${\beta}$-TCP)와 함께 임계결손부 크기의 두개결손부에 이식하였다. 모든 랫드는 골이식 수술 후 8주째에 희생되었으며, 골이식부의 골형성 능력은 일반방사선, micro CT 및 조직검사를 통해 평가되었다. ${\beta}$-TCP와 함께 이식된 골막유래세포는 골결손부에서 더욱 증가된 석회화작용을 나타내었으며, 골결손부 안쪽 및 가장자리에 골밀도 증가와 신생골이 형성되었다. 특히 골막유래세포는 ${\beta}$-TCP만 단독으로 이식하였을때보다 함께 이식 시 효과적으로 신생골을 형성하였다. 이러한 결과는 배양된 골막유래세포가 골결손부에서 골형성을 증진시킬 수 있는 가능성을 보였다.

• 대한한방내과학회지
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• 제36권4호
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• pp.518-526
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• 2015

Objectives This study investigated the effect of purified safflower (Carthamus tinctorius Linne) and safflower seed (Carthamus tinctorius L. seed; CS) extract, using hot water and ethanol extract methods , on the osteogenic differentiation of MC3T3E1 cells.Methods The safflower and safflower seed were extracted with hot water and ethanol. The samples were concentrated by a rotary evaporator and then freeze-dried using a freeze-dryer. The MC3T3E1 cells were propagated and maintained in DMEM (Gibco) containing 10% FBS and a 1% antibiotic antimycotic solution. To induce osteogenic differentiation, the cells were treated for 14 days with DMEM with 10 mM β-glycerophosphate and 50 μM ascorbic acid. Extract doses were confirmed by the results of an MTT assay, and treatment of the extracts was performed in a differentiation medium every two days. The ALP staining and activity were tested after osteogenic differentiation for five days, and after 14 days, osteogenic differentiation was determined by alizarin red S staining. The mRNA expressions of osteogenic-related genes were quantified using quantitative real-time PCR.Results In the results of the MTT assay, all concentrations of safflower extracts had no toxicity in the MC3T3El cells. But in the groups of 100 ng/ml and 200 ng/ml concentrations of safflower seed extracts, the cell viability was significantly reduced by up to 40-50%. So we fixed the treatment concentration of the extract at 50 ng/ml. In the ALP and alizarin red S staining, all extract groups increased osteogenic differentiation compared with the control group. The water-safflower extract group showed the highest mRNA level of Alp, Runx2, and Dlx5 genes. The mRNA level of Ocn, an osteogenic gene related to late-stage differentiation, in the ethanol-safflower extract group increased the mineralization more significantly than in other groups.Conclusions These data suggest that the extract of safflower increases the osteoblastic differentiation activates of MC3T3E1 cells like the extract of safflower seed. The water-extract and ethanol-extract of safflower have effects on different stages of osteogenesis in MC3T3El. Not only safflower seed but also safflower will be useful therapeutic reagents for age-associated chronic diseases such as osteoporosis.

• Journal of Periodontal and Implant Science
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• 제38권sup2호
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• pp.363-372
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• 2008

Purpose: This study compared the effects of coating implants with hydroxyapatite (HA) using an ion beam-assisted deposition (IBAD) method prepared with machined, anodized, sandblasted and large-grit acid etched (SLA) surfaces in minipigs, and verified the excellency of coating method with HA using IBAD. Material and Methods: 4 male Minipigs(Prestige World Genetics, Korea), 18 to 24 months old and weighing approximately 35 to 40 kg, were chosen. All premolars and first molars of the maxilla were carefully extracted on each side. The implants were placed on the right side after an 8 week healing period. The implant stability was assessed by resonance frequency analysis (RFA) at the time of placement. 40 implants were divided into 5 groups; machined, anodized, anodized plus IBAD, SLA, and SLA plus IBAD surface implants. 4 weeks after implantation on the right side, the same surface implants were placed on the left side. After 4 weeks of healing, the minipigs were sacrificed and the implants were analyzed by RFA, histology and histometric. Results: RFA showed a mean implant stability quotient (ISQ) of $75.625{\pm}5.021$, $76.125{\pm}3.739$ ISQ and $77.941{\pm}2.947$ at placement, after 4 weeks healing and after 8 weeks, respectively. Histological analysis of the implants demonstrated newly formed, compact, mature cortical bone with a nearby marrow spaces. HA coating was not separated from the HA coated implant surfaces using IBAD. In particular, the SLA implants coated with HA using IBAD showed better contact osteogenesis. Statistical and histometric analysis showed no significant differences in the bone to implant contact and bone density among 5 tested surfaces. Conclusion: We can conclude that rough surface implants coated with HA by IBAD are more biocompatible, and clinical, histological, and histometric analysis showed no differences when compared with the other established implant surfaces in normal bone.

• 대한치과교정학회지
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• 제38권1호
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• pp.13-30
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• 2008

하악 이부확장에서 골 절단선의 위치 및 종류와 견인 장치의 종류에 따른 차이를 알아보고자 삼차원 유한요소법으로 하악골의 이동 양상 및 응력 분포를 조사하였다. 골 견인장치의 종류로는 치아 의존형과 골 의존형, 혼합형, $30^{\circ}$ 기울여 위치한 치아 의존형의 4가지를, 골절단 위치와 방법으로 하악 중절치 간 수직절단과 하악 정중이부를 관통하는 계단식 골절단 등의 2가지를 설정하였다. 연구 결과, 골절단의 위치 및 방법과 견인장치의 종류에 관계없이 과두를 포함한 하악골의 모든 부위에서 외측방 변위를 보였으며 상하적이나 전후방적 변위는 적은 양이었으나 방향에 있어 군간에 차이를 보였다. 치아 의존형 장치에 의한 골절단면 이개 양태는 V형이었으나 골 의존형 장치는 역V형이고 혼합형 장치는 평행하게 확장되었다. 골 의존형 장치에 의한 하악각의 외측 변위량이 다른 장치에 비해 컸다. $30^{\circ}$ 기울여 위치한 치아 의존형에서의 변위는 측방적, 전후방적 면에서 좌우 차이가 인정되었다.

• Journal of Periodontal and Implant Science
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• 제32권1호
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• pp.89-112
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• 2002

The earliest reports of the use of electrical energy to directly stimulate bone healing seem to be in 1853 from England, the techniques involved the introduction of direct current into the non-united fracture site percutaneously via metallic needles, with subsequent healing of the defect. One endpoint of the periodontal therapy is to generate structure lost by periodontal diseases. Several procedural advances may support regeneration of attachment, however, regeneration of alveolar bone does not occur consistently. Therefore, factors which stimulate bone repair are areas for research in periodontal reconstructive therapy. Effects of cytokines or growth factors on bone repair are examples of such areas. Another one is electrical current which occurs in bone naturally, so that such bone may be particularly susceptible to electrical therapy. The purposes of this study were to observe the effects of electrical stimulation on the normal periodontium, to determine whether the electricity is the useful means for periodontal regeneration or not. Forty rats weighted about 100 gram were used and divided into 4 groups, the first group, there was no electrical stimulation with the connection of electrodes only. In the second group, there was stimulated by the 10 mA during 10 minutes per a day, in the third group was stimulated by the 25 mA , and the fourth by the 50 mA. At 3, 5, 10 and 15 days post-appliance , two rats in each group were serially sacrificed. and the maxillae and the mandible processed to paraffin, and the specimens were prepared with Hematoxylin-Eosin stain for the light microscopic evaluation. The results of this study were as follows : 1. There was the distinct reversal line on the lingual alveolar crest, whereas a little changes in the labial alveolarcrest to the duration and amount of currents. 2. In 50 mA group, the cells were highly concentrated at the apex of anterior teeth, and was observed the necrotic tissue. In posterior root apex, the hypercementosis was appeared, and newly formed cementum layer has been increased continuously with the time. 3. The periodontal ligament fiber and Sharpey's fiber were arranged in order, and the bone trabeculae were increased as the experiment proceeded by, relatively the bone marrows were decreased. 4. In the pulp tissue, the blood vessels were increased with blood congestion in the experimetal specimens remarkably, and the dentinal tubules were obstructed . 5. The osteoblasts in alveolar bone proper had been showed highly activity, and also observed the formation of bone trabeculea. In the conclusion, it was suggested that the electrical stimulation has influence on the periodontium and the pulp tissue. However, there might be the injurious effects.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제28권5호
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• pp.417-433
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• 2006

Purpose : Platelet rich plasma (PRP) is an autologous material with many growth factors, such as BMPs, PDGF, $TGF-{\beta}_1$, $TGF-{\beta}_2$, VEGF, and IGF, facilitating bone healing process. The prominent osteoconductive activity and the biodegradable nature of beta-tricalciumphosphate (${\beta}-TCP$) for bone grafts in animal experiments have been reported. The purpose of this study was to evaluate the effect of PRP on the osteogenesis of ${\beta}-TCP$. Materials & Methods : Two artificial calvarial bone defects were made in 32 rabbits which were divided into 2 groups. In one group of 16 rabbits, autogenous bone / ${\beta}-TCP$ was grafted on each side of cranial bone defect. In the other group of 16 rabbits, mixture of ${\beta}-TCP$ and PRP / PRP alone was grafted on each side of the cranial bone defect. The animals were sacrificed at 2, 4, 8, and 12 weeks after surgery. The specimens were harvested and examined histologically and immunohistochemically by the expression of BMP2/4/7, PDGF, VEGF and $TGF-{\beta}_1$. Results : The mean volume of new bone formation was significantly higher at 4, 8, 12 weeks in autogenous graft than that in ${\beta}-TCP$. The BMP2/4 expression was significantly higher at 4 weeks in autogenous bone graft and at 4 weeks in mixture of ${\beta}-TCP$ and PRP and at 12 weeks in ${\beta}-TCP$. The expression of BMP7, PDGF, VEGF and $TGF-{\beta}_1$ showed no significant difference in autogenous, ${\beta}-TCP$, mixture of ${\beta}-TCP$ and PRP, and PRP alone during grafted bone regeneration. Conclusion : The results showed that PRP had no additional value in promoting healing process of ${\beta}-TCP$ grafts.