1.New conceptual approaches toward dentin regeneration using the drug repositioning strategy with Wnt signaling pathways
Eui-Seon LEE ; Tae-Young KIM ; Yam Prasad ARYAL ; Kihyun KIM ; Seongsoo BYUN ; Dongju SONG ; Yejin SHIN ; Dany LEE ; Jooheon LEE ; Gilyoung JUNG ; Seunghoon CHI ; Yoolim CHOI ; Youngkyun LEE ; Chang-Hyeon AN ; Jae-Young KIM
International Journal of Oral Biology 2021;46(2):67-73
This study summarizes the recent cutting-edge approaches for dentin regeneration that still do not offer adequate solutions. Tertiary dentin is formed when odontoblasts are directly affected by various stimuli. Recent preclinical studies have reported that stimulation of the Wnt/β-catenin signaling pathway could facilitate the formation of reparative dentin and thereby aid in the structural and functional development of the tertiary dentin. A range of signaling pathways, including the Wnt/β-catenin pathway, is activated when dental tissues are damaged and the pulp is exposed. The application of small molecules for dentin regeneration has been suggested as a drug repositioning approach. This study reviews the role of Wnt signaling in tooth formation, particularly dentin formation and dentin regeneration. In addition, the application of the drug repositioning strategy to facilitate the development of new drugs for dentin regeneration has been discussed in this study.
2.New conceptual approaches toward dentin regeneration using the drug repositioning strategy with Wnt signaling pathways
Eui-Seon LEE ; Tae-Young KIM ; Yam Prasad ARYAL ; Kihyun KIM ; Seongsoo BYUN ; Dongju SONG ; Yejin SHIN ; Dany LEE ; Jooheon LEE ; Gilyoung JUNG ; Seunghoon CHI ; Yoolim CHOI ; Youngkyun LEE ; Chang-Hyeon AN ; Jae-Young KIM
International Journal of Oral Biology 2021;46(2):67-73
This study summarizes the recent cutting-edge approaches for dentin regeneration that still do not offer adequate solutions. Tertiary dentin is formed when odontoblasts are directly affected by various stimuli. Recent preclinical studies have reported that stimulation of the Wnt/β-catenin signaling pathway could facilitate the formation of reparative dentin and thereby aid in the structural and functional development of the tertiary dentin. A range of signaling pathways, including the Wnt/β-catenin pathway, is activated when dental tissues are damaged and the pulp is exposed. The application of small molecules for dentin regeneration has been suggested as a drug repositioning approach. This study reviews the role of Wnt signaling in tooth formation, particularly dentin formation and dentin regeneration. In addition, the application of the drug repositioning strategy to facilitate the development of new drugs for dentin regeneration has been discussed in this study.
3.Maxillary complete denture rehabilitation in flabby tissue patient considering of function and stability: A clinical report
Youngkyun CHOI ; Younghoo LEE ; Seoung-Jin HONG ; Janghyun PAEK ; Kwantae NOH ; Ahran PAE ; Hyeong-Seob KIM ; Kung-Rock KWON
The Journal of Korean Academy of Prosthodontics 2021;59(4):422-430
It is very difficult to achieve denture support, stability and retention in single-maxillary complete denture patients with flabby tissue. A 57-year-old male patient was uncomfortable with the existing denture and wanted treatment. The reduction of flabby tissue was confirmed using the treatment denture. Non-pressure impression was obtained using an intraoral scanner during the definitive denture process. This is reported because the resulting denture improved when observing the retention, support and stability of the denture during occlusion.
4.Alteration of cellular events in tooth development by chemical chaperon, Tauroursodeoxycholic acid treatment
Eui-Seon LEE ; Yam Prasad ARYAL ; Tae-Young KIM ; Elina POKHAREL ; Harim KIM ; Shijin SUNG ; Wern-Joo SOHN ; Youngkyun LEE ; Chang-Hyeon AN ; Jae-Young KIM
International Journal of Oral Biology 2020;45(4):190-196
Several factors, including genetic and environmental insults, impede protein folding and secretion in the endoplasmic reticulum (ER). Accumulation of unfolded or mis-folded protein in the ER manifests as ER stress. To cope with this morbid condition of the ER, recent data has suggested that the intracellular event of an unfolded protein response plays a critical role in managing the secretory load and maintaining proteostasis in the ER. Tauroursodeoxycholic acid (TUDCA) is a chemical chaperone and hydrophilic bile acid that is known to inhibit apoptosis by attenuating ER stress. Numerous studies have revealed that TUDCA affects hepatic diseases, obesity, and inflammatory illnesses. Recently, molecular regulation of ER stress in tooth development, especially during the secretory stage, has been studied. Therefore, in this study, we examined the developmental role of ER stress regulation in tooth morphogenesis using in vitro organ cultivation methods with a chemical chaperone treatment, TUDCA. Altered cellular events including proliferation, apoptosis, and dentinogenesis were examined using immunostaining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In addition, altered localization patterns of the formation of hard tissue matrices related to molecules, including amelogenin and nestin, were examined to assess their morphological changes. Based on our findings, modulating the role of the chemical chaperone TUDCA in tooth morphogenesis, especially through the modulation of cellular proliferation and apoptosis, could be applied as a supporting data for tooth regeneration for future studies.
5.Implications of specific gene expression patterns in enamel knot in tooth development
Tae-Young KIM ; Sanjiv NEUPANE ; Yam Prasad ARYAL ; Eui-Seon LEE ; Ji-Youn KIM ; Jo-Young SUH ; Youngkyun LEE ; Wern-Joo SOHN ; Seo-Young AN ; Jung-Hong HA ; Chang-Hyeon AN ; Jae-Young KIM
International Journal of Oral Biology 2020;45(1):25-31
Enamel knot (EK)—a signaling center—refers to a transient morphological structure comprising epithelial tissue. EK is believed to regulate tooth development in early organogenesis without its own cellular alterations, including proliferation and differentiation. EKs show a very simple but conserved structure and share functions with teeth of recently evolved vertebrates, suggesting conserved signaling in certain organs, such as functional teeth, through the course of evolution. In this study, we examined the expression patterns of key EK-specific genes including Dusp26 , Fat4, Meis2, Sln , and Zpld1 during mice embryogenesis. Expression patterns of these genes may reveal putative differentiation mechanisms underlying tooth morphogenesis.
6.Effects of an electric toothbrush combined with 3-color light-emitting diodes on antiplaque and bleeding control: a randomized controlled study
Chakyoung KWON ; Jae-Mok LEE ; Jo-Young SUH ; Seung-Jun SEO ; Youngkyun LEE ; Yong-Gun KIM
Journal of Periodontal & Implant Science 2020;50(4):251-259
Purpose:
This randomized controlled study aimed to evaluate the effects of an electric toothbrush with 3 colors of light-emitting diodes (LEDs) on antiplaque and bleeding control.
Methods:
This randomized, placebo-controlled, double-blinded, parallel-group clinical trial included 50 healthy adults with gingivitis, who were randomly assigned to 2 groups. The experimental group used electric toothbrushes with 3 colors of LEDs and the control group used the same electric toothbrush as the experimental group, but with LED sources with one-hundredth of the strength. The subjects used the electric toothbrush 3 times a day for 4 minutes each time. As clinical indices, bleeding on marginal probing (BOMP), the LöeSilness gingival index (GI), and the Turesky-Quigley-Hein plaque index (QHI) were assessed at baseline, at 3 weeks, and at 6 weeks.
Results:
There were significant decreases in all clinical indices (BOMP, GI, QHI) in both the experimental and control groups compared to baseline at 3 weeks and at 6 weeks. In a comparison between the experimental and control groups, no statistically significant differences were observed for any clinical indices at 3 weeks (P>0.05). However, at 6 weeks, statistically significant differences were observed between the experimental and control groups in BOMP and GI, which are indicators of gingival inflammation (P<0.05).
Conclusions
This study demonstrated that an electric toothbrush combined with 3-color LEDs reduced gingival bleeding and inflammation after 6 weeks.
7.Sodium Chloride Aggravates Arthritis via Th17 Polarization.
Seung Min JUNG ; Youngkyun KIM ; Juryun KIM ; Hyerin JUNG ; Hyoju YI ; Yeri Alice RIM ; Narae PARK ; Seung Ki KWOK ; Sung Hwan PARK ; Ji Hyeon JU
Yonsei Medical Journal 2019;60(1):88-97
PURPOSE: Sodium chloride (NaCl) has been proposed as a driving factor in autoimmune diseases through the induction of pathogenic CD4+ T helper cells that produce interleukin-17 (Th17 cells). This study investigated the effects of NaCl on inflammatory arthritis in mice and humans. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) mice were fed a normal or high-salt diet ad libitum, and clinical and histologic features of arthritis were evaluated. The proportion of Th17 cells in the spleens of CIA mice fed a normal or high-salt diet was evaluated by flow cytometry, and the expression of IL-17 in joints and intestines was determined by immunohistochemical staining. We also analyzed the effect of NaCl on Th17 differentiation from peripheral blood monocytes of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and evaluated the contents of sodium and IL-17 in the synovial fluid of RA and OA patients. RESULTS: NaCl increased murine and human Th17 cell differentiation in a dose-dependent manner. Clinical and histological arthritis was more severe in the high-salt-fed CIA mice, compared to control CIA mice. The proportion of Th17 cells among splenocytes was higher in CIA mice fed a high-salt diet. Expression of synovial and intestinal IL-17 was also higher in high-salt-fed CIA mice. Comparison of synovial fluid between RA patients and OA patients revealed that Na+ and IL-17 were more abundant in RA synovial fluid. CONCLUSION: This study suggests that NaCl can aggravate arthritis by affecting Th17 differentiation. Accordingly, limiting salt intake may be helpful for treating inflammatory arthritis, such as RA.
Animals
;
Arthritis*
;
Arthritis, Experimental
;
Arthritis, Rheumatoid
;
Autoimmune Diseases
;
Diet
;
Flow Cytometry
;
Humans
;
Interleukin-17
;
Intestines
;
Joints
;
Mice
;
Monocytes
;
Osteoarthritis
;
Sodium Chloride*
;
Sodium*
;
Spleen
;
Synovial Fluid
;
T-Lymphocytes, Helper-Inducer
;
Th17 Cells
8.The antiplaque and bleeding control effects of a cetylpyridinium chloride and tranexamic acid mouth rinse in patients with gingivitis.
Ji Eun LEE ; Jae Mok LEE ; Youngkyun LEE ; Jin Woo PARK ; Jo Young SUH ; Heung Sik UM ; Yong Gun KIM
Journal of Periodontal & Implant Science 2017;47(3):134-142
PURPOSE: This study aimed to evaluate the effects of a cetylpyridinium chloride (CPC) and tranexamic acid (TXA) mouth rinse on patients with gingivitis. METHODS: This randomized, placebo-controlled, double-blind, parallel-group, clinical trial included 45 healthy adults with gingivitis, who were randomized into 2 groups. The experimental group used a 0.05% CPC and 0.05% TXA mouth rinse, and the control group used a placebo mouth rinse. The following clinical indices were assessed at baseline, at 3 weeks, and at 6 weeks: the Turesky-Quigley-Hein plaque index (QHI), the Löe-Silness gingival index (GI), and bleeding on marginal probing (BOMP). The subjects used the mouth rinse during the experimental period for 20 seconds, 4–5 times daily (10 mL each time). RESULTS: There were no significant differences in the clinical indices between the groups at baseline. In the experimental group (CPC+TXA), a statistically significant improvement was evident in the QHI, GI, and BOMP at 3 and 6 weeks. These results were similar to those observed in the control group at 3 and 6 weeks, although the change in BOMP was not statistically significant in that group. At 6 weeks, the experimental group had a significantly lower mean score for the QHI than the control group. CONCLUSIONS: This study demonstrated that a CPC and TXA mouth rinse exhibited significant antiplaque and anti-gingivitis efficacy, and had a positive effect on bleeding control when used daily for 6 weeks.
Adult
;
Cetylpyridinium*
;
Dental Plaque Index
;
Gingivitis*
;
Hemorrhage*
;
Humans
;
Mouth*
;
Periodontal Index
;
Tranexamic Acid*
9.Effects of Escherichia Coli-derived Recombinant Human Bone Morphogenetic Protein-2 Loaded Porous Hydroxyaptite-based Ceramics on Calvarial Defect in Rabbits.
Shin Young KIM ; Youngkyun LEE ; Seung Jun SEO ; Jae Hong LIM ; Yong Gun KIM
Journal of Bone Metabolism 2017;24(1):23-30
BACKGROUND: Recombinant human bone morphogenetic proteins (rhBMPs) have been widely used in regenerative therapies to promote bone formation. The production of rhBMPs using bacterial systems such as Escherichia coli (E. coli) is estimated to facilitate clinical applications by lowering the cost without compromising biological activity. In clinical practice, rhBMP-2 and osteoconductive carriers (e.g., hydroxyapatite [HA] and bovine bone xenograft) are used together. This study examined the effect of E. coli-derived rhBMP-2 combined with porous HA-based ceramics on calvarial defect in rabbits. METHODS: Six adult male New Zealand white rabbits were used in this study. The experimental groups were divided into the following 4 groups: untreated (NC), bovine bone graft (BO), porous HA (HA) and porous HA with rhBMP-2 (HA-BMP). Four transosseous defects of 8 mm in diameter were prepared using stainless steel trephine bur in the frontal and parietal bones. Histological and histomorphometric analyses at 4 weeks after surgery revealed significant new bone formation by porous HA alone. RESULTS: HA-BMP showed significantly higher degree of bone formation compared with BO and HA group (P<0.05). The average new bone formation % (new bone area per total defect area) of NC, BO, HA, and HA-BMP at 4-week after surgery were 12.65±5.89%, 29.63±6.99%, 28.86±6.17% and 49.56±8.23%, respectively. However, there was no statistical difference in the bone formation between HA and BO groups. CONCLUSIONS: HA-BMP promoted more bone formation than NC, BO and HA alone. Thus, using E. coli-derived rhBMP-2 combined with porous HA-based ceramics can promote new bone formation.
Adult
;
Bone Morphogenetic Proteins
;
Ceramics*
;
Durapatite
;
Escherichia coli
;
Escherichia*
;
Humans*
;
Hydroxyapatites
;
Male
;
Osteogenesis
;
Parietal Bone
;
Rabbits*
;
Stainless Steel
;
Transplants
10.Eupatilin Ameliorates Collagen Induced Arthritis.
Juryun KIM ; Youngkyun KIM ; Hyoju YI ; Hyerin JUNG ; Yeri Alice RIM ; Narae PARK ; Seung Min JUNG ; Sung Hwan PARK ; Ji Hyeon JU
Journal of Korean Medical Science 2015;30(3):233-239
Eupatilin is the main active component of DA-9601, an extract from Artemisia. Recently, eupatilin was reported to have anti-inflammatory properties. We investigated the anti-arthritic effect of eupatilin in a murine arthritis model and human rheumatoid synoviocytes. DA-9601 was injected into collagen-induced arthritis (CIA) mice. Arthritis score was regularly evaluated. Mouse monocytes were differentiated into osteoclasts when eupatilin was added simultaneously. Osteoclasts were stained with tartrate-resistant acid phosphatase and then manually counted. Rheumatoid synoviocytes were stimulated with TNF-alpha and then treated with eupatilin, and the levels of IL-6 and IL-1beta mRNA expression in synoviocytes were measured by RT-PCR. Intraperitoneal injection of DA-9601 reduced arthritis scores in CIA mice. TNF-alpha treatment of synoviocytes increased the expression of IL-6 and IL-1beta mRNAs, which was inhibited by eupatilin. Eupatilin decreased the number of osteoclasts in a concentration dependent manner. These findings, showing that eupatilin and DA-9601 inhibited the expression of inflammatory cytokines and the differentiation of osteoclasts, suggest that eupatilin and DA-9601 is a candidate anti-inflammatory agent.
Animals
;
Anti-Inflammatory Agents/pharmacology/*therapeutic use
;
Arthritis, Experimental/chemically induced/*drug therapy
;
Arthritis, Rheumatoid/drug therapy/pathology
;
Cell Differentiation/*drug effects
;
Cells, Cultured
;
Collagen Type II
;
Cytokines/biosynthesis
;
Disease Models, Animal
;
Drugs, Chinese Herbal/therapeutic use
;
Female
;
Flavonoids/pharmacology/*therapeutic use
;
Humans
;
Inflammation/drug therapy/immunology
;
Interleukin-1beta/genetics/metabolism
;
Interleukin-6/genetics/metabolism
;
Lymph Nodes/cytology
;
Mice
;
Mice, Inbred DBA
;
Monocytes/cytology
;
Osteoclasts/*cytology
;
Plant Extracts/pharmacology
;
RNA, Messenger/biosynthesis
;
Synovial Membrane/cytology
;
T-Lymphocytes, Regulatory/cytology/immunology
;
Tumor Necrosis Factor-alpha/pharmacology

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