• BMB Reports
• /
• v.54 no.5
• /
• pp.266-271
• /
• 2021

Estrogen-related receptor γ (ERRγ), a member of the orphan nuclear receptor family, is a key mediator in cellular metabolic processes and energy homeostasis. Therefore, ERRγ has become an attractive target for treating diverse metabolic disorders. We recently reported that ERRγ acts as a negative regulator of osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In the present study, we explored the effects of an ERRγ-specific modulator, GSK5182, on ERRγ-regulated osteoclast differentiation and survival. Interestingly, GSK5182 increased ERRγ protein levels much as does GSK4716, which is an ERRγ agonist. GSK5182 inhibited osteoclast generation from bone-marrow-derived macrophages without affecting cytotoxicity. GSK5182 also attenuated RANKL-mediated expression of cFos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), pivotal transcription factors for osteoclastogenesis. Arrested osteoclast differentiation was associated with reduced RANK expression, but not with the M-CSF receptor, c-Fms. GSK5182 strongly blocked the phosphorylation of IκBα, c-Jun N-terminal kinase, and extracellular signal-regulated kinase in response to RANKL. GSK5182 also suppressed NF-κB promoter activity in a dose-dependent manner. In addition to osteoclastogenesis, GSK5182 accelerated osteoclast apoptosis by caspase-3 activation. Together, these results suggest that GSK5182, a synthetic ERRγ modulator, may have potential in treating disorders related to bone resorption.

• The korean journal of orthodontics
• /
• v.27 no.2
• /
• pp.335-347
• /
• 1997

Vitamin D is known to exert its action by activating DNA and RBA within target cells to produce proteins and enzymes that can be used in bone resorption process. Particularly, the active form of vitmain D, 1,25-dihydroxycholecalciferol $[1,25-(OH)_2D_3]$, is considered to be one of the most potent stimulators of osteoclatic acitivity in vitro. The purpose of this study was to evaluate the effect of 1,25-Dihydroxyvitamin $D_3$ on the avtivity of periodotal ligament cells and, the experimental tooth movement. Human periodontal ligament cells were collected from the first premolar tooth extracted for the orthodontic treatment, and were incubated in the environment of $37^{\circ}C$, 5% $CO_2$ and 95% humidity. Microtitration(MIT) assay was done at 10, 25, 50 and 100ng/ml of 1,25-Dihydroxyvitamin $D_3$. 21 Sprague-Daft rats were divided into a control gmup(3), and experimental groups(18) where 100g of force from helical spring was applied across the maxillary incisors 1,25-Dihydroxyvitamin $D_3$ was injected into periodontal ligament at the mesial or distal surface of maxillary incisors so that we can compare the control side and the experimental side. Expreimental groups were sac rifled at 12, 24, 36, 48, 72hours and 7 days after force application, respectively. And the obtained tissues were evaluated histologically. The observed results were as follows. 1. The activity of periodontal ligament cells in l0ng/ml or 25ng/ml of 1,25-Dihydroxyvitamin $D_3$ 1,25-Dihydroxyvitamin $D_3$ was not significantly different to the control at the cultivation of 1, 2 and 3 days. 2. The activity of periodontal ligament cells was significantly increased at 3 days in 50 ng/ml of 1,25-Dihydroxyvitamin $D_3$ and 2, 3 days in 100g/ml of 1,25-Dihydroxyvitamin $D_3$. 3. Up to 7 days after force application, there was no difference in osteoblastic activity, tearing of periodontal ligament and proliferation of capillary at tension side between 1,25-Dihydroxyvitamin $D_3$ injection side and the control side. 4. The osteoclastic activity and the resorption of alveolar bone was greater in 1,25-Dihydroxyvitamin $D_3$ injection side than the control side at 36 hours after force application.

• Journal of Periodontal and Implant Science
• /
• v.26 no.3
• /
• pp.605-624
• /
• 1996

Various bonegraft materials and the technique of guided tissue regeneration have been used to regenerate lost periodontal tissue. Calcium sulfate has been known as a bone graft material because of good biocompatibility, rapid resorption and effective osteoinduction. It has been known that calcium sulfate works as a binder to stabilize the defect when it is used with synthetic graft materials. The effects on the regeneration of pericxiontal tissue were studied in dogs after grafting 3-wall intrabony defects with calcium carbonate and calcium sulfate and covering with calcium sulfate barrier. The 3-wall intrabony defectstdmm width, 4mm depth, 4mm length) were created in anterior area and treated with flap operation alone(contol group), with porous resorbable calcium carbonate graft alonetexperirnental group 1), with calcium sulfate graft alonetexperimental group 2) and with composite graft of 80% calcium carbonate and 20% calcium sulfate with calcium sulfate barriertexperimental group 3). Healing responses were histologically observed after 8 weeks and the results were as follows: 1. The alveolar bone formation was $0.59{\pm}0.19mm$ in the control group, $1.80{\pm}0.25mm$ in experimental group 1, $1.61{\pm}0.21mm$ in experimental group 2 and $1.94{\pm}0.11mm$ in experimental group 3 with statistically significant differences between control group and all experimental groups(P<0.05). There were statistically significant differences between experimental group 1 and group 2 (P<0.05). 2. The new cementum formation was $0.48{\pm}0.19mm$ in the control group. $1.72{\pm}0.26mm$ in experimental group 1, $1.43{\pm}0.17mm$ in experimental group 2, $1.89{\pm}0.15mm$ in experimental group 3 with statiscally significant differences between control group and all experimental groups (p<0.05). There were statistically significant differences between experimental group 1 and group 2, and between experimental group 2 and group 3(P<0.05). 3. The length of junctional epithelium was $1.61{\pm}0.20mm$ in the contol group, $0.95{\pm}0.06mm$ in experimental group 1, $1.34{\pm}0.16mm$ in experimental group 2, $1.08{\pm}0.11mm$ in experimental group 3 with statiscally significant differences between control group and experimental group 1. and btween control group and experimental group 3(p<0.05). There were statistically significant differences between experimental group 1 ,and group 2, and between experimental group 2 and group 3(P<0.05). 4. The connective tissue adhesion was $1.67{\pm}O.20mm$ in the control group, $1.33{\pm}0.24mm$ in experimental group 1. $1.23{\pm}0.16mm$ in experimental group 2, $1.08{\pm}0.14mm$ in experimental group 3 with statistically significant differences between control group and all experimental groups(p<0.05). There were nostatistically significant differences between all experimental groups. As a result, epithelial migration was not prevented when calcium sulfate was used alone, but new bone and cementum formation were enhanced. Epithelial migration was prevented and new bone and cementum formation were also enhanced when calcium carbonate was used alone and when both calcium carbonate and calcium sulfate were used.

• The Journal of the Korean bone and joint tumor society
• /
• v.15 no.2
• /
• pp.111-121
• /
• 2009

Background: Osteosarcoma is one of the most common primary malignant tumors of bone occurring mainly in children and adolescents. Although surgery combined with chemotherapy has markedly improved patient survival during the last years, the use of anticancer drugs is still associated with serious problem, such as the frequent acquisition of drug-resistant phenotypes and occurrence of "secondary malignancies". Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and recently clinical trials have been initiated on MMP-inhibitors. On the other hand, bisphosphonates (BPs) are inhibitors of bone resorption, and widely used to treat osteoclast-mediated bone diseases. Also they appear to possess direct antitumor activity. Methods: One osteosarcoma cell line (U2OS) was treated with ibandronate (0, 0.1, 1, $10{\mu}M$) for 48 hours. Cell viabilities were determined using MTT assay, the mRNA levels of MMP-2 and MT1-MMP were detected by reverse-transcription polymerase chain reaction, the amount of MMP-2 and MT1-MMP protein were measured by Westernblot, the activities of MMP-2 were observed by Gelatin zymography, and Matrigel invasion assays were used to investigate the invasive potential of osteosarcoma cell lines before and after ibandronate treatment. Results: The invasiveness of U2OS cell line was reduced dose-dependently following 48 hour treatment of up to $10{\mu}M$ of the ibandronate at which concentration no cytotoxicity occurred. Furthermore, the gelatinolytic activities and protein and mRNA levels of MMP-2 and MT1-MMP were also suppressed by increasing ibandronate concentrations. Conclusion: Given that MMP-2 is instrumental in tumor cell invasion, it is very likely that the reduction in osteosarcoma cell invasion by ibandronate is a consequence, at least in part, of suppressed expression of both MMP-2 and MT1-MMP. Isolation of a molecule (s) responsible for the bisphosphonate inhibition of tumor cell invasion would pave the way for the development of a new generation of metastasis inhibitors.

• The korean journal of orthodontics
• /
• v.25 no.4
• /
• pp.403-414
• /
• 1995

The purpose of this study was to investigate the histologic changes in mandibular periodontium during overbite closure for openbite treatment by continuous arch wires and anterior vertical elastics. Two female monkey(Macaca nemestrina) with permanent dentition were used. Posterior bite block was fixed to each of their maxillae, which made the animal temporary anterior openbite as well as stabilized the whole maxillary anchorage. In each mandible, all the teeth except the second molars which had been extracted, were prepared for cast crowns. 018 inch Standard brackets were welded on these crowns. After cementation, two types of the $016{\times}022$ inch continuous arch wires, the plain ideal arch to the control animal and the MEAW(multiloop edgewise archwire) to the other experimental one were inserted. Then anterior vertical elastics were applied for two weeks. The overbite depth changes in the monkeys and histologic examinations of the mandibular periodontiums suggested the following conclusions. 1. During two weeks of the experimental period, the overbite increased + 0.3 mm in the control and + 1.3 mm in the experimental one. 2. In both the control and the experimental animal, histologic examinations showed that incisors, canines and first premolars were subject to extrusive force and the rest of posteriors were subject to intrusive one. 3. In periodontiums of the extruded incisors of the experimental one, reorientation of the periodontal fiber structures reflected the direction of force and the alveolar bone surfaces including apical and crestal areas which had been subject to tension, were the front of new bone formation. 4. In periodontiums of the extruded incisors of the experimental one, neither excessive hyalinization nor gross root resorption was observed. 5. Alveolar bone remodeling of anteriors and posteriors was more remarkable in the experimental one than the control.

• The Journal of Korean Academy of Prosthodontics
• /
• v.49 no.1
• /
• pp.29-37
• /
• 2011

Purpose: In cases when implant supported overdenture is made by using standard size implant, additional procedure such as bone surgery and bone grafting can be required. And it gives burden to doctor and patient in terms of cost. Therefore, it is necessary to find the implant therapy for the edentulous patients in making denture with accordable cost and simple procedure. Materials and methods: Edentulous patients with upper and lower dentures participated in this study. Before the operation, survey about patient's satisfaction to the existing dentures was carried out. Surgical procedures included four small diameter implants installation anterior area and immediate loading. One and three month after the procedure, the same survey about patient's satisfaction was carried out, and radiography was taken. Results: We are doing research to the nine patients. Survival rate is 97.2 percent. The comparison of patient's satisfaction before and after surgery is performed based on oral health impact profile 49. We analyze mainly with masticatory discomfort, retention, aesthetics, social problem, psychological discomfort problems. As a result, satisfaction level is increased at all factors. Retention is the most increased satisfactory factor followed by mastication difficulty, pronunciation, psychological discomfort, social discomfort, aesthetics in order. Marginal bone loss is 0.21 mm at 12 weeks after implant placement. Conclusion: This research reveals that the denture supported by mini dental implant increases patient's satisfaction. This study will be continued with more patients for a long time and we are scheduled for taking additional radiography to check whether peri-implant bone resorption occurs or not.

• Journal of Periodontal and Implant Science
• /
• v.35 no.4
• /
• pp.1019-1037
• /
• 2005

The major goals of periodontal therapy are the functional regeneration of periodontal supporting structures already destructed by periodontal disease as well as the reduction of signs and symptoms of progressive periodontal disease. There have been many efforts to develop materials and therapeutic methods to promote periodontal wound healing. There have been increasing interest on the chitosan made by chtin. Chitosan is a derivative of chitin made by deacetylation of side chains. Chitosan has been widely studied as bone substitution and membrane material in periodontology. Many experiments using chitosan in various animal models have proven its beneficial effects. Tetracycline has been considered for use in the treatment of chronic periodontal disease and gingivitis. The aim of this study is to evlauate the osteogenesis of tetracycline blended chitosan membranes on the calvarial critical size defect in Sprague Dawley rats. An 8mm surgical defect was produced with a trephine bur in the area of the midsagittal suture. The rats were divided into five groups: Untreated control group versus four experimental group. Four types of membranes were made and comparative study was been done. Two types of non-woven membranes were made by immersing non-woven chitosan into either the tetracycline solution or chitosan-tetracycline solution. Other two types of sponge membranes were fabricated by immersing chitosan sponge into the tetracycline solution, and subsequent freeze-drying. The animals were sacrificed at 2 and 8 weeks after surgical procedure. The specimens were examined by histologic analyses. The results are as follows: 1. Clinically the use of tetracycline blended chitosan membrane showed great healing capacity. 2. The new bone formations of all the experimental group, non-woven and sponge type membranes were greater than those of control group. But, there was no significant difference between the experimental groups. 3. Resorption of chitosan membranes were not shown in any groups at 2 weeks and 8 weeks. These results suggest that the use of tetracycline blended chitosan membrane on the calvarial defects in rats has significant effect on the regeneration of bone tissue in itself. And it implicate that tetracycline blended chitosan membrane might be useful for guided tissue regeneration.

• The korean journal of orthodontics
• /
• v.28 no.1 s.66
• /
• pp.165-174
• /
• 1998

The turnover of collagen is controlled by the balance between collagen synthesis and degradation. The production of collagenase (matrix metalloproteinase-1) and its inhibitor, tissue inhibitor of matrix metallopmteinase-1 (TIMP-1) are one of the substances which regulate this balance. The periodontal ligament fibroblast plays an important role in collagen metabolism during orthodontic treatment and is believed to be an origin of the osteoblast in the alveolar bone. The collagenase secreted by the periodontal ligament fibroblast and the osteoblast initiates the bone resorption by removing the osteoid layer in the alveloar bone. The interleukin-$1{\beta}$ is secreted by the macrophage during orthodontic treatment. The present study was undertaken to assess the effect of mechanical stress and interleukin-$1{\beta}$ on the expression of collagenase and TIMP-1 in the periodontal ligament fibroblasts using reverse transcription polymerase chain reaction and immunohistochemical staining. The periodontal ligament fibroblasts were stitched by placing the $Petriperm dish^{\circledR}$ dish on the top of spheroidal convex watch glass ($5\%$ surface increase) and tented with interleukin-$1{\beta}$ (1.0 ng/ml), or treated with both of them. Treatment with mechanical stress and/or interleukin-$1{\beta}$ resulted in increased collagenase mRNA expression. The mechanical stress treated group (1.61, 1.62, 1.37 fold increase), the interleukin-$1{\beta}$, tented group (1.68, 1.60, 3.78 fold increase), the mechanical stress and interleukin-$1{\beta}$ treated group (1.89, 1.72, 5.48 fold increase) induced increases in collagenase mRNA compared with the control group after 2, 4, 8 hours respectively. But TIMP-1 mRNA expressions at experimental groups were decreased after 2, 4 hours and increased after 8 hours. The mechanical stress treated group (0.16, 0.49 fold decrease and 3.77 fold increase), the interleukin-$1{\beta}$ treated group (0.15,0.44 fold decrease and 4.46 fold increase), the mechanical stress and interleukin-$1{\beta}$ tented group (0.15, 0.69 fold decrease and 4.81 fold increase) induced changes in TIMP-1 mRNA compared with the control group after 2, 4, 8 hours, respectively. Immunohistochemical stain showed that increased collagenase and TIMP-1 staining of the mechanical stress tented group, the interleukin-$1{\beta}$ treated group, and the mechanical stress and interleukin-$1{\beta}$ treated group compared with that of the control group after 8 hours. These findings suggest that mechanical stress and interleukin-$1{\beta}$ regulate expression of collagenase and TIMP-1.

• Journal of Periodontal and Implant Science
• /
• v.26 no.3
• /
• pp.641-654
• /
• 1996

In infectious disease, invasion of host tissue by bacteria or their products frequently induces a wide variety of inflammatory and immunopathologic reaction. Evidence indicates that cytokines are involved in the initiation and progression of chronic inflammatory diseases, such as periodontitis. Interleukin-6, which is a multifunctional cytokine, has important roles in acute and chronic inflammation and may also be implicated in bone resorption. Periodontal diseases are characterized by chronic inflammation of the periodontium with alveolar bone resoption. A principal driving force behind this response appears to lie in the immune system's response to bacteria. Many of the cell components which have been shown to function as virulence factors in gram-negative bacteria are associated with the bacterial surface. Of these, lipopolysaccharide has been characterized as one that mediates a number of biological activities which can lead to the destruction of host tissue. Non-steroidal antiinflammatory drug is used for reduce inflammation, and most of NSAIDs inhibit prostaglandine $E_2$ production, but it is shown that $PGE_2$ production is stimulated by IL-1 in recent study. So, the influence of other cytokines except $PGE_2$ on periodontium can not be avoided. Therefore, new antiinflammatory drug is needed. Rhizoma coptidis is used in oriental medicine for anti-inflammation and antiseptics. In this present study, we examined the IL-6 release in periodontal ligament cells treated with the lipopolysaccharide, and also the effect of rhizoma coptidis on cellular activity and IL-6 production of periodontal ligament cells. To evaluate the effect of rhizoma coptidis on cellular activity, the cells were seeded at a cell density of $1{\times}10^4$ cells/well in 24-well culture plates. After one day incubation, 1-6, 10-9 and 10-12 g/ml of rhizoma coptidis and 5, $10{\mu}g/ml$ of LPS were added to the each well and incubated for 1 and 2 days, respectively. Then, MTT assay were carried out. To evaluate the effect of rhizoma coptidis on IL-6 production, the cells were seeded at a cell density of $1.5{\times}10^4$ cells/well in 24-well culture plates. After one day incubation, 10-9 g/ml of rhizoma coptidis and 5, $10{\mu}g/ml$ of LPS were added to the each well and incubated for 3, 6, 12 and 24 hours. Then, amounts of IL-6 production is measured by IL-6 ELISA kit used. The results were as follows : 1. Rhizoma coptidisrbelow to ($10^{-6}g/ml$) significantly increaed cellular activity of periodontal ligament cells than control. 2. Rhizoma coptidist ($10^{-9}g/ml$) significantly increased cellular activity of LPS($5{\mu}g/ml$)-treated periodontal ligament cells than control. 3. LPS(5 and $10{\mu}g/ml$) significantly increased IL-6 production of periodontal ligament cells than control. 4. Rhizoma coptidis($10^{-9}g/ml$) decreased IL-6 production of LPS ($5{\mu}g/ml$)-treated periodontal.ligarnent cells than LPS only tested group. These findings suggest that stimulation of the IL-6 release of periodontal ligament cells by LPS may have a role in the progression of inflammation and alveolar bone resoption in periodontal disease, and that inhibition of the IL-6 release of cells and stimulation of cellular activity by rhizoma coptidis may help the periodontal regeneration.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
• /
• v.22 no.2
• /
• pp.223-234
• /
• 1992

The purpose of this study was to investigate the changes of periodontal tissues in the irradiated mandibular bone in rats which were fed normal diet and low calcium diet In order to carry out this experiment, 64 seven-week old Sprague-Dawley strain rats weighing about 150gms were selected and equally divided into one experimental group of 32 rats and one control group with the remainder. The experimental group and the control group were then subdivided into two groups when the rats reached the age of 10 weeks, 16 rats were allotted for each subdivided group was composed of 16 rats and exposed to irradiation. The two groups were irradiated a single dose of 20Gy on the only jaw area and irradiated with a cobalt-60 teletherapy unit The rats in the control and experimental groups were serially dissected by fours on the 3rd, the 7th, the 14th, and the 21st day after irradiation. After each dissection, both sides of the dead rat mandibular bodies were removed and fixed with 10% neutral formalin. The specimens sectioned and observed in histopathological. histochemical. and immunocellular chemical methods. The obtained results were as follows: 1. In the mandibles of rats with low calcium diet the increased number of fibroblasts of periodontal ligaments. many small capillaries and irregular arrangement of loose collagen fibers were detected and the partial resorption of dentin and cementum could be found by the microscopic studies. 2. In the group of irradiated rats, degenerated periodontal tissues led to the condition of irregular arrangement of collagen fibers and the decreased number of fibroblasts. But this condition was somewhat restored after 21 days of experiment. 3. Periodontal tissues of the irradiated rat group with low calcium diet were destroyed earlier than those of the irradiated rat group with normal diet. Soon this condition was restored and then high cellularity and dense collagen fibers were observed. 4. Many periodontal cells bearing tumor necrosis factor could be clearly observed in the nonirradiated group of rats with normal diet, whereas could not be observed on the 7th day and reappeared on 14th day in the irradiated group of rats with normal diet. A few of them could be observed in the group of rats with low calcium diet, but they could be clearly observed in the both groups after 21 days of experiment.