Protective effects of red orange (Citrus sinensis L. Osbeck Rutaceae) extract against UVA-B radiation-induced photoaging in Skh:HR-2 mice

BACKGROUND/OBJECTIVES@#The skin is the outermost organ of the human body and plays a protective role against external environmental damages, such as sunlight and pollution, which affect anti-oxidant defenses and skin inflammation, resulting in erythema or skin reddening, immunosuppression, and epidermal DNA damage.MATERIALS/METHODS: The present study aimed to investigate the potential protective effects of red orange complex H extract (ROC) against ultraviolet (UV)-induced skin photoaging in Skh:HR-2 mice. ROC was orally administered at doses of 20, 40, and 80 mg/ kg/day for 13 weeks, along with UV irradiation of the mice for 10 weeks. @*RESULTS@#ROC improved UV-induced skin barrier parameters, including erythema, melanin production, transepidermal water loss, elasticity, and wrinkle formation. Notably, ROC inhibited the mRNA expression of pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor α) and melanogenesis. In addition, ROC recovered the UV-induced decrease in the hyaluronic acid and collagen levels by enhancing genes expression. Furthermore, ROC significantly downregulated the protein and mRNA expression of matrix metalloproteinases responsible for collagen degradation. These protective effects of ROC against photoaging are associated with the suppression of UV-induced phosphorylation of c-Jun NH2-terminal kinase and activator protein 1 activation. @*CONCLUSIONS@#Altogether, our findings suggest that the oral administration of ROC exerts potential protective activities against photoaging in UV-irradiated hairless mice.

Fracture Liaison Service in Korea: 2022 Position Statement of the Korean Society for Bone and Mineral Research

Osteoporosis and osteoporotic fractures cause socioeconomic concerns, and medical system and policies appear insufficient to prepare for these issues in Korea, where the older adult population is rapidly increasing. Many countries around the world are already responding to osteoporosis and osteoporotic fractures by adopting fracture liaison service (FLS), and such an attempt has only begun in Korea. In this article, we introduce the operation methods for institutions implementing FLS and characteristics of services, and activities of the FLS Committee for FLS implementation in the Korean Society for Bone and Mineral Research. In addition, we hope that the current position statement will contribute to the implementation of FLS in Korea and impel policy changes to enable a multidisciplinary and integrated FLS operated under the medical system.

Gynostemma pentaphyllum extract and Gypenoside L enhance skeletal muscle differentiation and mitochondrial metabolism by activating the PGC-1α pathway in C2C12 myotubes

BACKGROUND/OBJECTIVES@#Peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α) has a central role in regulating muscle differentiation and mitochondrial metabolism. PGC-1α stimulates muscle growth and muscle fiber remodeling, concomitantly regulating lactate and lipid metabolism and promoting oxidative metabolism.Gynostemma pentaphyllum (Thumb.) has been widely employed as a traditional herbal medicine and possesses antioxidant, anti-obesity, anti-inflammatory, hypolipemic, hypoglycemic, and anticancer properties. We investigated whether G. pentaphyllum extract (GPE) and its active compound, gypenoside L (GL), affect muscle differentiation and mitochondrial metabolism via activation of the PGC-1α pathway in murine C2C12 myoblast cells.MATERIALS/METHODS: C2C12 cells were treated with GPE and GL, and quantitative reverse transcription polymerase chain reaction and western blot were used to analyze the mRNA and protein expression levels. Myh1 was determined using immunocytochemistry.Mitochondrial reactive oxygen species generation was measured using the 2′7′-dichlorofluorescein diacetate assay. @*RESULTS@#GPE and GL promoted the differentiation of myoblasts into myotubes and elevated mRNA and protein expression levels of Myh1 (type IIx). GPE and GL also significantly increased the mRNA expression levels of the PGC-1α gene (Ppargc1a), lactate metabolismregulatory genes (Esrra and Mct1), adipocyte-browning gene fibronectin type III domaincontaining 5 gene (Fndc5), glycogen synthase gene (Gys), and lipid metabolism gene carnitine palmitoyltransferase 1b gene (Cpt1b). Moreover, GPE and GL induced the phosphorylation of AMP-activated protein kinase, p38, sirtuin1, and deacetylated PGC-1α. We also observed that treatment with GPE and GL significantly stimulated the expression of genes associated with the anti-oxidative stress response, such as Ucp2, Ucp3, Nrf2, and Sod2/i>. @*CONCLUSIONS@#The results indicated that GPE and GL enhance exercise performance by promoting myotube differentiation and mitochondrial metabolism through the upregulation of PGC-1α in C2C12 skeletal muscle.

Operational Definition Identifying Osteoporotic Vertebral Fractures in the Claims Database

Background@#We analyzed the International Classification of Diseases, 10th edition (ICD-10) diagnostic codes, procedure codes, and radiographic image codes for vertebral fracture (VF) used in the database of Health Insurance Review and Assessment Service (HIRA) of Korea to establish a validated operational definition for identifying patients with osteoporotic VF in claims data. @*Methods@#We developed three operational definitions for detecting VFs using 9 diagnostic codes, 5 procedure codes and 4 imaging codes. Medical records and radiographs of 2,819 patients, who had primary and subordinated codes of VF between January 2016 and December 2016 at two institutions, were reviewed to detect true vertebral fractures. We evaluated the sensitivity and positive predictive value (PPV) of the operational definition in detecting true osteoporotic VF and obtained the receiver operating characteristic (ROC) curve. @*Results@#Among the 2,819 patients who had primary or secondary diagnosis codes for VF, 995 patients satisfied at least one of the criteria for the operational definition of osteoporotic VF. Of these patients, 594 were judged as having true fractures based on medical records and radiographic examinations. The sensitivity and PPV were 62.5 (95% confidence interval [CI], 59.4–65.6) and 59.7(95% CI, 56.6–62.8) respectively. In the receiver operating characteristic analysis, area under the curve (AUC) was 0.706 (95% CI, 0.688–0.724). @*Conclusion@#Our findings demonstrate the validity of our operational definitions to identify VFs more accurately using claims data. This algorithm to identify VF is likely to be useful in future studies for diagnosing osteoporotic VF.

Gynostemma pentaphyllum extract and its active component gypenoside L improve the exercise performance of treadmill-trained mice

BACKGROUND/OBJECTIVES@#The effectiveness of natural compounds in improving athletic ability has attracted attention in both sports and research. Gynostemma pentaphyllum (Thunb.) leaves are used to make traditional herbal medicines in Asia. The active components of G.pentaphyllum, dammarane saponins, or gypenosides, possess a range of biological activities. On the other hand, the anti-fatigue effects from G. pentaphyllum extract (GPE) and its effective compound, gypenoside L (GL), remain to be determined.MATERIALS/METHODS: This study examined the effects of GPE on fatigue and exercise performance in ICR mice. GPE was administered orally to mice for 6 weeks, with or without treadmill training. The biochemical analysis in serum, glycogen content, mRNA, and protein expressions of the liver and muscle were analyzed. @*RESULTS@#The ExGPE (exercise with 300 mg/kg body weight/day of GPE) mice decreased the fat mass percentage significantly compared to the ExC mice, while the ExGPE showed the greatest lean mass percentage compared to the ExC group. The administration of GPE improved the exercise endurance and capacity in treadmill-trained mice, increased glucose and triglycerides, and decreased the serum creatine kinase and lactate levels after intensive exercise. The muscle glycogen levels were higher in the ExGPE group than the ExC group. GPE increased the level of mitochondrial biogenesis by enhancing the phosphorylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein and the mRNA expression of nuclear respiratory factor 1, mitochondrial DNA, peroxisome proliferatoractivated receptor-δ, superoxide dismutase 2, and by decreasing the lactate dehydrogenase B level in the soleus muscle (SOL). GPE also improved PGC-1α activation in the SOL significantly through AMPK/p38 phosphorylation. @*CONCLUSIONS@#These results showed that GPE supplementation enhances exercise performance and has anti-fatigue activity. In addition, the underlying molecular mechanism was elucidated. Therefore, GPE is a promising candidate for developing functional foods and enhancing the exercise capacity and anti-fatigue activity.

Lateral Decubitus Position for Pediatric Nd:YAG Laser Capsulotomy under General Anesthesia

Purpose@#To report a successful case of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy performed in a noncompliant pediatric patient using the lateral decubitus position and a conventional slit-lamp-based laser system under general anesthesia.Case summary: Progression of a thick posterior capsular opacity with associated vision loss (best-correct visual acuity of 0.1) was detected in a nine-year-old child with a past history of cataract surgery in his right eye. Diagnosed with pediatric uveitis at the age of five, he had been treated previously using a combination of topical and systemic corticosteroids, which led to the development of the cataract and subsequent surgery 16 months later. Severe photophobia prevented outpatient-based laser treatment, and the patient underwent our modified procedure. Under general anesthesia, the patient was placed in a lateral decubitus position with the use of a long intubation tube. The height of the bed and table-based laser system was adjusted so as to minimize strain when positioning the child’s head. Successful laser capsulotomy was performed within 10 minutes, and the entire anesthesia time was less than 30 minutes. The patient experienced immediate improvement in symptoms, showing a visual acuity of 1.0, which has been sustained as of his most recent visit, 3 months postoperatively. The patient experienced no ocular or anesthesia- related complications. @*Conclusions@#Nd:YAG laser capsulotomy performed by careful positioning (lateral decubitus) under general anesthesia is a viable strategy for the safe and efficient removal of posterior capsular opacities in children with poor compliance.

Osteonecrosis of the Femoral Head: an Updated Review of ARCO on Pathogenesis, Staging and Treatment

Non-traumatic osteonecrosis of the femoral head (ONFH) usually affects adults younger than 50 years and frequently leads to femoral head collapse and subsequent arthritis of the hip.It is becoming more prevalent along with increasing use of corticosteroids for the adjuvant therapy of leukemia and other myelogenous diseases as well as management of organ transplantation. This review updated knowledge on the pathogenesis, classification criteria, staging system, and treatment of ONFH.

Incidence and Risk of Venous Thromboembolism in Bisphosphonates and Selective Estrogen Receptor Modulators Treatment in Korea

Background@#Selective estrogen receptor modulators (SERMs) were associated with an increased risk of venous thromboembolism (VTE) due to the estrogen effect. In this study, we investigated the effect of SERMs on VTE compared to bisphosphonates (BPs) using the Korean National Health Insurance claims database. @*Methods@#This was a retrospective cohort study. Women over 50 years old who were first prescribed BPs or SERMs for osteoporosis treatment in 2012 were included. The difference in VTE incidence between the SERMs and BP groups was compared. Both groups were followed up for VTE or PE occurrence, death, or until December 2016. The study population was analyzed by 3:1 matching according to age using a multivariate Cox model. @*Results@#The hazard ratio (HR) for VTE was 0.72 (95% confidence interval [CI], 0.40–1.28) in the SERMs group compared to BP group. Older age (60–69 vs. 50–59 years: HR, 3.77; 95% CI, 2.07–6.86 and 70–79 vs. 50–59 years: HR, 5.88; 95% CI, 3.14–11.02), major osteoporotic fracture (HR, 1.77; 95% CI, 1.16- 2.70), atrial fibrillation (HR, 3.31; 95% CI, 1.35–8.11), and estrogen replacement (HR, 3.40; 95% CI, 2.01–5.73) all increased VTE risk. In subgroup analysis of the SERMs group, past hospitalization (HR, 2.24; 95% CI, 1.02–4.92), estrogen replacement (HR, 5.75; 95% CI, 2.29–14.39), and glucocorticoid replacement (HR, 2.71; 95% CI, 1.05–7.0) increased VTE risk. @*Conclusion@#SERMs did not increase the risk of VTE compared to BPs in Koreans with osteoporosis. However, old age and estrogen replacement both increased VTE risk.

New conceptual approaches toward dentin regeneration using the drug repositioning strategy with Wnt signaling pathways

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.

Development of a Risk Score for QT Prolongation in the Intensive Care Unit Using Time-Series Electrocardiogram Data and Electronic Medical Records / 대한의료정보학회지

Objectives@#Drug-induced QT prolongation can lead to life-threatening arrhythmia. In the intensive care unit (ICU), various drugs are administered concurrently, which can increase the risk of QT prolongation. However, no well-validated method to evaluate the risk of QT prolongation in real-world clinical practice has been established. We developed a risk scoring model to continuously evaluate the quantitative risk of QT prolongation in real-world clinical practice in the ICU. @*Methods@#Continuous electrocardiogram (ECG) signals measured by patient monitoring devices and Electronic Medical Records data were collected for ICU patients. QT and RR intervals were measured from raw ECG data, and a corrected QT interval (QTc) was calculated by Bazett’s formula. A case-crossover study design was adopted. A case was defined as an occurrence of QT prolongation ≥12 hours after any previous QT prolongation. The patients served as their own controls. Conditional logistic regression was conducted to analyze prescription, surgical history, and laboratory test data. Based on the regression analysis, a QTc prolongation risk scoring model was established. @*Results@#In total, 811 ICU patients who experienced QT prolongation were included in this study. Prescription information for 13 drugs was included in the risk scoring model. In the validation dataset, the high-risk group showed a higher rate of QT prolongation than the low-and low moderate-risk groups. @*Conclusions@#Our proposed model may facilitate risk stratification for QT prolongation during ICU care as well as the selection of appropriate drugs to prevent QT prolongation.

Lateral Decubitus Position for Pediatric Nd:YAG Laser Capsulotomy under General Anesthesia

Purpose@#To report a successful case of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy performed in a noncompliant pediatric patient using the lateral decubitus position and a conventional slit-lamp-based laser system under general anesthesia.Case summary: Progression of a thick posterior capsular opacity with associated vision loss (best-correct visual acuity of 0.1) was detected in a nine-year-old child with a past history of cataract surgery in his right eye. Diagnosed with pediatric uveitis at the age of five, he had been treated previously using a combination of topical and systemic corticosteroids, which led to the development of the cataract and subsequent surgery 16 months later. Severe photophobia prevented outpatient-based laser treatment, and the patient underwent our modified procedure. Under general anesthesia, the patient was placed in a lateral decubitus position with the use of a long intubation tube. The height of the bed and table-based laser system was adjusted so as to minimize strain when positioning the child’s head. Successful laser capsulotomy was performed within 10 minutes, and the entire anesthesia time was less than 30 minutes. The patient experienced immediate improvement in symptoms, showing a visual acuity of 1.0, which has been sustained as of his most recent visit, 3 months postoperatively. The patient experienced no ocular or anesthesia- related complications. @*Conclusions@#Nd:YAG laser capsulotomy performed by careful positioning (lateral decubitus) under general anesthesia is a viable strategy for the safe and efficient removal of posterior capsular opacities in children with poor compliance.

Osteonecrosis of the Femoral Head: an Updated Review of ARCO on Pathogenesis, Staging and Treatment

Non-traumatic osteonecrosis of the femoral head (ONFH) usually affects adults younger than 50 years and frequently leads to femoral head collapse and subsequent arthritis of the hip.It is becoming more prevalent along with increasing use of corticosteroids for the adjuvant therapy of leukemia and other myelogenous diseases as well as management of organ transplantation. This review updated knowledge on the pathogenesis, classification criteria, staging system, and treatment of ONFH.

Incidence and Risk of Venous Thromboembolism in Bisphosphonates and Selective Estrogen Receptor Modulators Treatment in Korea

Background@#Selective estrogen receptor modulators (SERMs) were associated with an increased risk of venous thromboembolism (VTE) due to the estrogen effect. In this study, we investigated the effect of SERMs on VTE compared to bisphosphonates (BPs) using the Korean National Health Insurance claims database. @*Methods@#This was a retrospective cohort study. Women over 50 years old who were first prescribed BPs or SERMs for osteoporosis treatment in 2012 were included. The difference in VTE incidence between the SERMs and BP groups was compared. Both groups were followed up for VTE or PE occurrence, death, or until December 2016. The study population was analyzed by 3:1 matching according to age using a multivariate Cox model. @*Results@#The hazard ratio (HR) for VTE was 0.72 (95% confidence interval [CI], 0.40–1.28) in the SERMs group compared to BP group. Older age (60–69 vs. 50–59 years: HR, 3.77; 95% CI, 2.07–6.86 and 70–79 vs. 50–59 years: HR, 5.88; 95% CI, 3.14–11.02), major osteoporotic fracture (HR, 1.77; 95% CI, 1.16- 2.70), atrial fibrillation (HR, 3.31; 95% CI, 1.35–8.11), and estrogen replacement (HR, 3.40; 95% CI, 2.01–5.73) all increased VTE risk. In subgroup analysis of the SERMs group, past hospitalization (HR, 2.24; 95% CI, 1.02–4.92), estrogen replacement (HR, 5.75; 95% CI, 2.29–14.39), and glucocorticoid replacement (HR, 2.71; 95% CI, 1.05–7.0) increased VTE risk. @*Conclusion@#SERMs did not increase the risk of VTE compared to BPs in Koreans with osteoporosis. However, old age and estrogen replacement both increased VTE risk.

New conceptual approaches toward dentin regeneration using the drug repositioning strategy with Wnt signaling pathways

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.

Development of a Risk Score for QT Prolongation in the Intensive Care Unit Using Time-Series Electrocardiogram Data and Electronic Medical Records / 대한의료정보학회지

Objectives@#Drug-induced QT prolongation can lead to life-threatening arrhythmia. In the intensive care unit (ICU), various drugs are administered concurrently, which can increase the risk of QT prolongation. However, no well-validated method to evaluate the risk of QT prolongation in real-world clinical practice has been established. We developed a risk scoring model to continuously evaluate the quantitative risk of QT prolongation in real-world clinical practice in the ICU. @*Methods@#Continuous electrocardiogram (ECG) signals measured by patient monitoring devices and Electronic Medical Records data were collected for ICU patients. QT and RR intervals were measured from raw ECG data, and a corrected QT interval (QTc) was calculated by Bazett’s formula. A case-crossover study design was adopted. A case was defined as an occurrence of QT prolongation ≥12 hours after any previous QT prolongation. The patients served as their own controls. Conditional logistic regression was conducted to analyze prescription, surgical history, and laboratory test data. Based on the regression analysis, a QTc prolongation risk scoring model was established. @*Results@#In total, 811 ICU patients who experienced QT prolongation were included in this study. Prescription information for 13 drugs was included in the risk scoring model. In the validation dataset, the high-risk group showed a higher rate of QT prolongation than the low-and low moderate-risk groups. @*Conclusions@#Our proposed model may facilitate risk stratification for QT prolongation during ICU care as well as the selection of appropriate drugs to prevent QT prolongation.

Effectiveness of Transfer Learning for Deep Learning-Based Electrocardiogram Analysis / 대한의료정보학회지

Objectives@#Many deep learning-based predictive models evaluate the waveforms of electrocardiograms (ECGs). Because deep learning-based models are data-driven, large and labeled biosignal datasets are required. Most individual researchers find it difficult to collect adequate training data. We suggest that transfer learning can be used to solve this problem and increase the effectiveness of biosignal analysis. @*Methods@#We applied the weights of a pretrained model to another model that performed a different task (i.e., transfer learning). We used 2,648,100 unlabeled 8.2-second-long samples of ECG II data to pretrain a convolutional autoencoder (CAE) and employed the CAE to classify 12 ECG rhythms within a dataset, which had 10,646 10-second-long 12-lead ECGs with 11 rhythm labels. We split the datasets into training and test datasets in an 8:2 ratio. To confirm that transfer learning was effective, we evaluated the performance of the classifier after the proposed transfer learning, random initialization, and two-dimensional transfer learning as the size of the training dataset was reduced. All experiments were repeated 10 times using a bootstrapping method. The CAE performance was evaluated by calculating the mean squared errors (MSEs) and that of the ECG rhythm classifier by deriving F1-scores. @*Results@#The MSE of the CAE was 626.583. The mean F1-scores of the classifiers after bootstrapping of 100%, 50%, and 25% of the training dataset were 0.857, 0.843, and 0.835, respectively, when the proposed transfer learning was applied and 0.843, 0.831, and 0.543, respectively, after random initialization was applied. @*Conclusions@#Transfer learning effectively overcomes the data shortages that can compromise ECG domain analysis by deep learning.

Inhibition of Interleukin-4 and β-Hexosaminidase Release in RBL-2H3 Cells by Compounds Isolated from Lobelia chinensis

Lobelia chinensis Lour. has commonly been used in traditional Chinese medicine for the treatment of antidote, diuretic, diarrhea, and inflammation. This study aimed to identify the active compounds in an aqueous extract of L. chinensis responsible for its anti-atopic effect in vitro using RBL-2H3 cells. A chemical investigation of secondary metabolites in an aqueous extract of L. chinensis led to the isolation of nine chemical constituents, which included the four marker compounds, and these were evaluated for their inhibitory effects on IL-4 mRNA expression and the release of β-hexosaminidase in propidium iodide-induced RBL-2H3 cells. We found diosmetin and fraxidin inhibited cellular IL-4 mRNA expression, and that diosmetin and 6,8-dimethoxycoumarin inhibited DNP-specific IgE-induced degranulation in these cells. Our study suggests that diosmetin, fraxidin, and 6,8-dimethoxycoumarin are potential candidates for the treatment of atopic diseases.

Osteoporosis and Osteoporotic Fracture Fact Sheet in Korea

Background@#The socioeconomic burdens of osteoporosis and related fractures have increased in parallel with population aging. The Korea Society of Bone and Mineral Research published fact sheets on these topics in 2017, 2018, and 2019. This study provides complied epidemiological data based on these fact sheets for understanding current status of osteoporosis in Korea. @*Methods@#Data from the Korea National Health and Nutrition Examination Survey (2008-2011) performed by the Korea Centers for Disease Control and Prevention and from National Health Information database (2008-2016) by National Health Insurance Service of Korea was used for analyzing the prevalence and incidence of osteoporosis and related fractures, respectively, fatality rates after fractures, and prescription status of anti-osteoporotic medications (AOMs). @*Results@#Among Korean adults aged ≥50 years, 22.4% and 47.9% had osteopenia or osteoporosis, respectively. Incidences of osteoporotic hip, vertebral, humerus, and distal radius fractures plateaued in 2013. The cumulative incidence of subsequent fractures gradually increased over 4 years of follow-up once an osteoporotic fracture occurred. Crude fatality rates in the first 12 months after hip fracture were 14.0% for women and 21.0% for men. Only 33.5% of patients with osteoporosis took AOMs, and even after an osteoporotic fracture, only 41.9% of patients took AOMs within the following 12 months. Despite a steady increase in AOM prescriptions of ~6% per annum, only 33.2% of patients were medication compliant (medication possession ratio ≥80%) at 12 months after treatment initiation. @*Conclusions@#Continuous efforts are required to diagnose patients at high risk of fracture and ensure proper management in Korea.

Alteration of cellular events in tooth development by chemical chaperon, Tauroursodeoxycholic acid treatment

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.

Implications of specific gene expression patterns in enamel knot in tooth development

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.