• 대한한의학회지
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• 제34권3호
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• pp.69-85
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• 2013

Objectives: This study investigated the anti-osteoarthritic effects of Kyejiinsam-tang (hereinafter referred to KIT) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods: Anti-oxidative effects of KIT were measured by scavenging activities of DPPH, reactive oxygen species (ROS) and nitric oxide (NO). Scavenging activities of anti-oxidation in lipopolysaccharide (LPS)-treated RAW 264.7 cells were also measured for inhibitory effects against the production of inflammatory mediators (tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, interleukin-6). Osteoarthritis was induced in rats by injecting MIA in the knee joint. Rats were divided into a total of 4 groups (n=6). The normal group were not treated at all without inducing osteoarthritis whereas the control group were induced for osteoarthritis by MIA and oral medicated physiological saline per day. The positive comparison group was injected with MIA and after 7 days, 2 mg/kg of Indomethacin. The experimental group was injected with MIA and after 7 days was medicated with 34 mg/kg of KIT. Indomethacin and KIT were orally-medicated for each substance a total of 4 weeks, once per day. Weight-bearing on hind legs was measured every week after MIA injection. At the end of the experiment (5 weeks after MIA injection), micro CT (computed tomography)-arthrography and histopathological examinations on the articular structures of knee joint were performed. The effect on inflammatory cytokines and immunological cells in synovial fluid was measured. Volume of cartilage was measured by micro CT-arthrography. Injury to synovial tissue was measured by H & E (hematoxylin and eosin), Safranin-O immunofluorescence. Results: 1. Cytotoxicity against hFCs was insignificant. 2. KIT showed the potent full term for DPPH. 1. NO was significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and ROS was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 2. IL-6 and IL-$1{\beta}$ were significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and TNF-${\alpha}$ was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 1. In hind legs weight-bearing measurement, level of weight increased. 2. Functions of liver and kidney were not affected. 3. IL-$1{\beta}$ was significantly reduced and TNF-${\alpha}$, IL-6 were also reduced but not significantly. 4. PGE2 (prostaglandin E2), LTB4 (leukotriene B4) were significantly reduced in the KIT group. 5. MMP-9 (matrix metalloproteinase-9), TIMP-1 (tissue inhibitor of metalloproteinases-1) and Osteocalcin were significantly reduced in the KIT group. 6. Destruction of cartilage on micro CT arthrography was reduced but had no significant differences. 7. Histopathologically, injury to synovial membrane of the KIT group was decreased and proteoglycan content of KIT group was increased. Conclusions: According to this study, Kyejiinsam-tang has inhibiting effect on the progression of arthritis in MIA-induced osteoarthritis rat. Kyejiinsam-tang has anti-oxidants and anti-inflammation effects, and is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

• Journal of the Optical Society of Korea
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• 제20권5호
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• pp.607-613
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• 2016

The pleura is known as an end target organ of exposure to toxic environmental materials such as fine particulate matter and asbestos. Moreover, long-term exposure to hazardous materials can eventually lead to fatal lung disease such as diffuse pleural fibrosis or mesothelioma. Chest computed tomography (CT) and ultrasound are gold standard imaging modalities for detection of advanced pleural disease. However, a diagnostic tool for early detection of pleural reaction has not been developed yet due to difficulties in imaging ultra-fine structure of the pleura. Optical coherence tomography (OCT), which provides cross-sectional images of micro tissue structures at a resolution of 2-10 μm, can image the mesothelium with a thickness of ~100 μm and therefore enables investigation of the early pleural reaction. In this study, we induced the early pleural reaction according to a time sequence after pleurodesis using talc, which has been widely used in the clinical field. The pleural reaction in talc grouped according to the time sequence (1st, 2nd, 4th weeks) showed a significant thickening (average thickness: 45 ± 7.5 μm, 80 ± 10.7 μm, 90 ± 12.5 μm), while the pleural reaction in sham and normal groups showed pleural change from normal to minimal thickening (average thickness: 16 ± 5.5 μm, 17 ± 4.5 μm, 15 ± 6.5 μm, and 12 ± 7.5 μm, 13 ± 2.5 μm, 12 ± 3.5 μm). The measurement of pleural reaction by pathologic examinations was well-matched with the measurement by OCT images. This is the first study for measuring the thickness of pleural reactions using a biophotonic modality such as OCT. Our results showed that OCT can be useful for evaluating the early pleural reaction.

• 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.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제33권6호
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• pp.459-466
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• 2011

Purpose: This study evaluated the capability of bone formation with silk fibroin/nano-hydroxyapatite/corn starch composite scaffold as a bone defect replacement matrix when grafted in a calvarial bone defect of rabbits $in$ $vivo$. Methods: Ten New Zealand white rabbits were used for this study and bilateral round-shaped defects were formed in the parietal bone (diameter: 8.0 mm). The silk fibroin 10% nano-hydroxyapatite/30% corn starch/60% composite scaffold was grafted into the right parietal bone (experimental group). The left side (control group) was grafted with a nano-hydroxyapatite (30%)/corn starch (70%) scaffold. The animals were sacrificed at 4 weeks and 8 weeks. A micro-computerized tomography (${\mu}CT$) of each specimen was taken. Subsequently, the specimens were decalcified and stained with Masson's trichrome for histological and histomorphometric analysis. Results: The average ${\mu}CT$ and histomorphometric measures of bone formation were higher in the control group than in the experimental group at 4 weeks and 8 weeks after surgery though not statistically significant ($P$ >0.05). Conclusion: The rabbit calvarial defect was not successfully repaired by silk fibroin/nano-hydroxyapatite/corn starch composite scaffold and may have been due to an inflammatory reaction caused by silk powder. In the future, the development of composite bone graft material based on various components should be performed with caution.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제34권1호
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• pp.1-11
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• 2012

Purpose: The purpose of this study was to evaluate the bone regeneration capacity of silk fibroin (SF) when combined with beta tricalcium phosphate (${\beta}$-tricalcium phosphate [TCP]) and rh-bone morphogenetic protein (BMP) in vivo by micro-computed tomography (CT), soft x-ray, and histological analysis. Methods: A total of 56 critical size defects formed by a trephine bur made on 28 adult female Spague-Dawley rats were used for this study and the defect size was 5.0 mm in diameter. The defects were transplanted with (1) no graft material (raw defect), (2) autogenous bone, (3) SF ($10{\mu}g$), (4) SF-BMP ($10{\mu}g$, $0.8{\mu}g$ each), and (5) SF+${\beta}$-TCP ($10{\mu}g$). At 4 and 8 weeks after operation, the experimental animals were sacrificed. Samples were evaluated with soft x-ray, histological examinations and 3-dimensional micro-CT analysis. Results: In the 3-dimensional micro-CT evaluation, bone volume and bone surface data were higher in the SF-BMP ($12.8{\pm}1.5$, $138.6{\pm}45.0$ each) (P<0.05) and SF-TCP ($12.3{\pm}1.5$, $144.9{\pm}30.9$ each) group than in the SF group ($6.1{\pm}3.3$, $77.2{\pm}37.3$ each) (P<0.05), except for the autogenous group ($15.0{\pm}3.0$, $190.7{\pm}41.4$ each) at 4 weeks. At 8 weeks, SF-BMP ($16.8{\pm}3.5$, $173.9{\pm}34.2$ each) still revealed higher (P<0.05) bone volum and surface, but SF-TCP ($11.3{\pm}1.5$, $1132.9{\pm}52.1$ each) (P=0.5, P=0.2) revealed the same or lower amount compared with the SF group ($13.8{\pm}2.7$, $127.5{\pm}44.8$ each). The % of bone area determined by radiodensity was higher in the SF-TCP ($31.4{\pm}9.1%$) and SF-BMP ($36.2{\pm}16.2%$) groups than in the SF ($19.0{\pm}10.4$) group at the period of 4 weeks. Also, in the histological evaluation, the SF-BMP group revealed lower inflammation reaction, lower foreign body reaction and higher bone healing than the SF group at postoperative 4 weeks and 8 weeks. The SF-TCP group revealed lower inflammation at 4 weeks, but accordingly, as the TCP membrane was absorbed, inflammatory and foreign body reaction are increased at 8 weeks. Conclusion: The current study provides evidence that the silk fibrin can be used as an effective grafted material for tissue engineering bone generation through a combination of growth factor or surface treatment.

• 한국정밀공학회지
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• 제25권5호
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• pp.148-154
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• 2008

Pharmacotherapy was mainly used to treat osteoporosis. However, some researches showed that pharmacotherapy could induce unexpected adverse effects. Some studies showed that whole body vibration affected beneficially osteoporosis. This paper studied the effect of whole body vibration fur osteoporosis compared with the effect of pharmacotherapy. 10 female rats were used and allocated into 4 group, CON, SHAM, DRUG, and WBV. Rats except SHAM group were ovariectomised to induce osteoporosis. Rats in WBV group were stimulated in whole body vibration at magnitude of $1mm_{peak-peak}$ and frequency 45Hz, for 8 weeks (30 min/day, 5 days/week). Rat in DRGU group was orally administered the Actonel (0.58mg/Kg), for 8 weeks (5days/week). The $4^{th}$ lumbar in rats were scanned at a resolution of $35{\mu}m$ at baseline, before stimulation, and 8 weeks after stimulation by In-vivo micro computed tomography. For detecting and tracking changes of biomechanical characteristics (morphological and mechanical characteristics) in lumbar trabecuar bone of rats, structural parameters were measured and calculated from acquiring images and finite element analysis was performed. In the results, loss of quantity and change of structure of trabecular bone in WBV group were smaller than those in both CON and SHAM groups. In addition, mechanical strength in WBV group was stronger than that in both CON and SHAM groups. In contrast, biomechanical characteristics in WBV group were similar with those in DRUG group. These results showed that reasonable whole body vibration was likely to treat osteoporosis and be substituted partly for drug treatment.

• Journal of Microbiology and Biotechnology
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• 제31권10호
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• pp.1401-1408
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• 2021

This study examined whether the oral administration of low-molecular-weight collagen peptide (LMCP) containing 3% Gly-Pro-Hyp with >15% tripeptide (Gly-X-Y) content could ameliorate osteoarthritis (OA) progression using a rabbit anterior cruciate ligament transection (ACLT) model of induced OA and chondrocytes isolated from a patient with OA. Oral LMCP administration (100 or 200 mg/kg/day) for 12 weeks ameliorated cartilage damage and reduced the loss of proteoglycan compared to the findings in the ACLT control group, resulting in dose-dependent (p < 0.05) improvements of the OARSI score in hematoxylin & eosin (H&E) and Safranin O staining. In micro-computed tomography analysis, LMCP also significantly (p < 0.05) suppressed the deterioration of the microstructure in tibial subchondral bone during OA progression. The elevation of IL-1β and IL-6 concentrations in synovial fluid following OA induction was dose-dependently (p < 0.05) reduced by LMCP treatment. Furthermore, immunohistochemistry illustrated that LMCP significantly (p < 0.05) upregulated type II collagen and downregulated matrix metalloproteinase-13 in cartilage tissue. Consistent with the in vivo results, LMCP significantly (p < 0.05) increased the mRNA expression of COL2A1 and ACAN in chondrocytes isolated from a patient with OA regardless of the conditions for IL-1β induction. These findings suggest that LMCP has potential as a therapeutic treatment for OA that stimulates cartilage regeneration.

• Journal of Korean Neurosurgical Society
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• 제61권5호
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• pp.559-567
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• 2018

Objective : The aim of this study was to evaluate the effect for biodegradable screws containing bone morphogenetic protein-2 (BMP-2) in an osteoporotic rat model. Methods : Twenty-four female Wistar rat (250-300 g, 12 weeks of age) were randomized into four groups. Three groups underwent bilateral ovariectomy (OVX). Biodegradable screws with or without BMP-2 were inserted in the proximal tibia in two implantation groups. The extracted proximal metaphysis of the tibiae were scanned by exo-vivo micro-computed tomography. Evaluated parameters included bone mineral density (BMD), trabecular bone volume (BV/TV), trabecular number, trabecular thickness, and trabecular separation (Tb.Sp). The tibia samples were pathologically evaluated by staining with by Hematoxylin and Eosin, and trichrome. Results : Trabecular formation near screw insertion site was evident only in rats receiving BMP-2 screws. BMD and BV/TV significantly differed between controls and the OVX and OVX with screw groups. However, there were no significant differences between control and OVX with screw BMP groups. Tb.Sp significantly differed between control and OVX and OVX with screw groups (p<0.05), and between the OVX and OVX with screw BMP group (p<0.05), with no statistically significant difference between control and OVX with screw BMP groups. Over the 12 weeks after surgery, bone lamellae in direct contact with the screw developed more extensive and thicker trabecular bone around the implant in the OVX with screw BMP group compared to the OVX with screw group. Conclusion : Biodegradable screws containing BMP-2 improve nearby bone conditions and enhance ostoeintegration between the implant and the osteoporotic bone.

• 대한의용생체공학회:의공학회지
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• 제38권4호
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• pp.175-182
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• 2017

Microcurrent electrical stimulation(MES) has been used to accelerate recovery of atrophied skeletal muscle. However, convincing stimulation parameters for suppressing muscle atrophy due to injured sciatic nerve remains unclear. The objective of this study was to investigate the effective intensity of MES on restraining muscle atrophy with rat model underwent sciatic nerve injury(SNI). Twenty-5-week-old Sprague Dawley male rats were equally assigned to five groups : Control group(Control, CON, n = 4), Denervation group(Denervation, D, n = 4), Denervation with MES of $22{\mu}A$ group(Denervation + $22{\mu}A$, D+22, n = 4), Denervation with MES of $100{\mu}A$ group (Denervation + $100{\mu}A$, D+100 n = 4), Denervation with MES of $400{\mu}A$ group(Denervation + $400{\mu}A$, D+400, n = 4). To induce muscle atrophy, all rats in the D, D+22, D+100, and D+400 groups, were subjected to sciatic nerve injury on their right hindlimb and allowed to have 1 week of resting period. Following this period, rats underwent daily MES(60 min/ a day, 5times/1week) for 4 weeks. After that, we investigate morphological changes in muscle volume by using in vivo micro-computed tomography at week 0, 1, 3 and 5. After 5 weeks, the muscle volume had the highest value in D+400 group, and also noticeably increased in D+100 group compared to it in D group. The results of this study imply that MES with current intensities between $100-400{\mu}A$ can suppress muscle atrophy effectively.

• Journal of Periodontal and Implant Science
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• 제54권2호
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• pp.96-107
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• 2024

Purpose: Deproteinized bovine bone or synthetic hydroxyapatite are 2 prevalent bone grafting materials used in the clinical treatment of peri-implant bone defects. However, the differences in bone formation among these materials remain unclear. This study evaluated osteogenesis kinetics in peri-implant defects using 2 types of deproteinized bovine bone (Bio-Oss^® and Bio-Oss/Collagen^®) and 2 types of synthetic hydroxyapatite (Apaceram-AX^® and Refit^®). We considered factors including newly generated bone volume; bone, osteoid, and material occupancy; and bone-to-implant contact. Methods: A beagle model with a mandibular defect was created by extracting the bilateral mandibular third and fourth premolars. Simultaneously, an implant was inserted into the defect, and the space between the implant and the surrounding bone walls was filled with Bio-Oss, Bio-Oss/Collagen, Apaceram-AX, Refit, or autologous bone. Micro-computed tomography and histological analyses were conducted at 3 and 6 months postoperatively (Refit and autologous bone were not included at the 6-month time point due to their rapid absorption). Results: All materials demonstrated excellent biocompatibility and osteoconductivity. At 3 months, Bio-Oss and Apaceram-AX exhibited significantly greater volumes of formation than the other materials, with Bio-Oss having a marginally higher amount. However, this outcome was reversed at 6 months, with no significant difference between the 2 materials at either time point. Apaceram-AX displayed notably slower bioresorption and the largest quantity of residual material at both time points. In contrast, Refit had significantly greater bioresorption, with complete resorption and rapid maturation involving cortical bone formation at the crest at 3 months, Refit demonstrated the highest mineralized tissue and osteoid occupancy after 3 months, albeit without statistical significance. Conclusions: Overall, the materials demonstrated varying post-implantation behaviors in vivo. Thus, in a clinical setting, both the properties of these materials and the specific conditions of the defects needing reinforcement should be considered to identify the most suitable material.