Schisandrin C enhances odontoblastic differentiation through autophagy and mitochondrial biogenesis in human dental pulp cells

Takanche, Jyoti Shrestha,Kim, Jeong-Seok,Kim, Ji-Eun,Han, S-H.,Yi, Ho-Keun Elsevier 2018 Archives of oral biology Vol.88 No.-

<P><B>Abstract</B></P> <P><B>Objective</B></P> <P>To investigate the role of Schisandrin C in odontoblastic differentiation, and its relations between autophagy and mitochondrial biogenesis in human dental pulp cells (HPDCs).</P> <P><B>Design</B></P> <P>Fresh third molars were used, and cultured for HDPCs. Western blotting technique, Alizarin red S staining, alkaline phosphatase (ALP) activity, and confocal microscopy were used to detect autophagy, mitochondrial biogenesis, and odontoblastic differentiation. To understand the mechanism of Schisandrin C, the HDPCs were treated with lipopolysaccharide (LPS), autophagy and heme oxygenase-1 (HO-1) inhibitors: 3-Methyladenine (3-MA) and Zinc protoporphyrin IX (ZnPP), respectively.</P> <P><B>Results</B></P> <P>LPS decreased the expression of autophagy molecules [autophagy protein 5 (ATG-5), beclin-1, and microtubule-associated protein 1A/1B light chain 3 (LC3-I/II)] and mitochondrial biogenesis molecules [heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)], and disrupted odontoblastic differentiation. The down-regulation of autophagy and mitochondrial biogenesis with 3-MA and ZnPP inhibited odontoblastic differentiation. However, Schisandrin C restored the expression of all the above molecules, even with LPS and inhibitor treatment. This result demonstrates that autophagy and mitochondrial biogenesis plays an essential role in odontoblastic differentiation, and Schisandrin C activates these systems to promote odontoblastic differentiation of HDPCs.</P> <P><B>Conclusion</B></P> <P>Schisandrin C has potential characters to regulate odontoblastic differentiation, and may be recommended for use as a compound for pulp homeostasis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Autophagy and mitochondrial biogenesis are linked with odontoblastic differentiation. </LI> <LI> Schisandrin C promotes odontoblastic differentiation in HDPCs. </LI> <LI> It mediated this function via mitochondrial biogenesis and autophagy. </LI> </UL> </P>

Effect of gomisin A on osteoblast differentiation in high glucose-mediated oxidative stress

Takanche, Jyoti Shrestha,Kim, Ji-Eun,Han, Sin-Hee,Yi, Ho-Keun Elsevier 2020 Phytomedicine Vol.66 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Gomisin A is a lignan isolated from the hexane of <I>Schisandra chinensis</I> fruit extract with antioxidant properties. Oxidative stress mediated by high glucose is one of the major complications of diabetes mellitus.</P> <P><B>Purpose</B></P> <P>This study investigates the role of gomisin A in osteoblast differentiation under high glucose-induced oxidative stress in MC3T3 E1 cells and determines its relationship with heme oxygenase-1 (HO-1) and mitochondrial biogenesis.</P> <P><B>Methods</B></P> <P>MC3T3 E1 cells were treated by gomisin A following induced by high glucose levels and glucose oxidase to investigate the inhibitory effect of gomisin A against high glucose oxidative stress. Western blot analysis, alizarin red staining, alkaline phosphatase (ALP) activity, analysis of reactive oxygen species (ROS) and confocal microscopy were used to determine mitochondrial biogenesis, oxidative stress, osteoblast differentiation and mineralization. To analyze the role of HO-1, the MC3T3 E1 cells were treated with the HO-1 inhibitor zinc protoporphyrin IX (ZnPP).</P> <P><B>Results</B></P> <P>Gomisin A enhanced the expression of HO-1, increased mitochondrial biogenesis factors (peroxisome proliferator-activated receptor gamma coactivator 1–alpha, nuclear respiratory factor-1, and mitochondrial transcription factor A), antioxidant enzymes (copper-zinc superoxide dismutases and manganese superoxide dismutase), osteoblast differentiation molecules (bone morphogenic protein-2/7, osteoprotegerin and Runt-related transcription factor-2) and mineralization by upregulation of ALP and alizarin red staining, which were decreased by ZnPP and high glucose oxidative stress. Similarly, gomisin A inhibited ROS which was increased by ZnPP and the high glucose-mediated oxidative stress.</P> <P><B>Conclusions</B></P> <P>The findings demonstrated the antioxidative effects of gomisin A, and its role in mitochondrial biogenesis and osteoblast differentiation. It potentially regulated osteoblast differentiation under high glucose-induced oxidative stress <I>via</I> upregulation of HO-1 and maintenance of mitochondrial homeostasis. Thus, gomisin A may represent a potential therapeutic agent for prevention of bone fragility fractures and implant failure triggered by diabetes.</P> <P><B>Graphical abstarct</B></P> <P>[DISPLAY OMISSION]</P>

Insulin growth factor binding protein-3 enhances dental implant osseointegration against methylglyoxal-induced bone deterioration in a rat model

Takanche, Jyoti Shrestha,Kim, Ji-Eun,Jang, Sungil,Yi, Ho-Keun Korean Academy of Periodontology 2021 Journal of Periodontal & Implant Science Vol.51 No.-

Purpose: The aim of this study was to determine the effect of insulin growth factor binding protein-3 (IGFBP-3) on the inhibition of glucose oxidative stress and promotion of bone formation near the implant site in a rat model of methylglyoxal (MGO)-induced bone loss. Methods: An in vitro study was performed in MC3T3 E1 cells treated with chitosan gold nanoparticles (Ch-GNPs) conjugated with IGFBP-3 cDNA followed by MGO. An in vivo study was conducted in a rat model induced by MGO administration after the insertion of a dental implant coated with IGFBP-3. Results: MGO treatment downregulated molecules involved in osteogenic differentiation and bone formation in MC3T3 E1 cells and influenced the bone mineral density and bone volume of the femur and alveolar bone. In contrast, IGFBP-3 inhibited oxidative stress and inflammation and enhanced osteogenesis in MGO-treated MC3T3 E1 cells. In addition, IGFBP-3 promoted bone formation by reducing inflammatory proteins in MGO-administered rats. The application of Ch-GNPs conjugated with IGFBP-3 as a coating of titanium implants enhanced osteogenesis and the osseointegration of dental implants. Conclusions: This study demonstrated that IGFBP-3 could be applied as a therapeutic component in dental implants to promote the osseointegration of dental implants in patients with diabetes, which affects MGO levels.

Insulin growth factor binding protein-3 enhances dental implant osseointegration against methylglyoxal-induced bone deterioration in a rat model

Jyoti Shrestha Takanche,김지은,장성일,이호근 대한치주과학회 2022 Journal of Periodontal & Implant Science Vol.52 No.2

Purpose: The aim of this study was to determine the effect of insulin growth factor binding protein-3 (IGFBP-3) on the inhibition of glucose oxidative stress and promotion of bone formation near the implant site in a rat model of methylglyoxal (MGO)-induced bone loss. Methods: An in vitro study was performed in MC3T3 E1 cells treated with chitosan gold nanoparticles (Ch-GNPs) conjugated with IGFBP-3 cDNA followed by MGO. An in vivo study was conducted in a rat model induced by MGO administration after the insertion of a dental implant coated with IGFBP-3. Results: MGO treatment downregulated molecules involved in osteogenic differentiation and bone formation in MC3T3 E1 cells and influenced the bone mineral density and bone volume of the femur and alveolar bone. In contrast, IGFBP-3 inhibited oxidative stress and inflammation and enhanced osteogenesis in MGO-treated MC3T3 E1 cells. In addition, IGFBP-3 promoted bone formation by reducing inflammatory proteins in MGO-administered rats. The application of Ch-GNPs conjugated with IGFBP-3 as a coating of titanium implants enhanced osteogenesis and the osseointegration of dental implants. Conclusions: This study demonstrated that IGFBP-3 could be applied as a therapeutic component in dental implants to promote the osseointegration of dental implants in patients with diabetes, which affects MGO levels.

LPS로 유도된 Human Dental Pulp Cells에서 Schisandrin C 의 항염증 효과

Jyoti Shrestha Takanche,Sang Won Lee,Yae Jin Kim,Young Hee Lee,Jeong Seok Kim,Ji Eun Kim,Ho Keun Yi,Sin Hee Han 한국약용작물학회 2016 한국약용작물학술대회 발표집 Vol.2016 No.10

Background : Tooth vitality is reflected by the health of dental pulp. Schisandrin C is a natural compound extracted from the fruit of Schisandra chinensis which has anti-inflammatory and anti-oxidant properties. The role of Schisandrin C on human dental pulp cells (HDPCs) has not been studied yet. This study examined the properties of Schisandrin C as an anti-inflammatory and anti-oxidant compound, and whether its characteristics promote mitochondrial biogenesis in HDPCs. Methods and Results : HDPCs were extracted from fresh third molars and cultured. Reactive oxidative stress (ROS) and nitric oxide (NO) formation were analyzed by a Muse cell analyzer. Western blotting and gelatin zymography were used to identify the presence of anti-oxidants, as well as inflammatory and mitochondrial biogenesis. Confocal microscopy was used for the detection of mitochondrial activity. Schisandrin C inhibited lipopolysaccharide (LPS)-stimulated inflammatory molecules; intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), matrix metalloproteinase-2 and -9 (MMP-2/9), NO production, ROS formation and the mitogen-activated protein (MAPK) pathway through minimizing the nuclear factor kappa B (NF-kB) translocation. Schisandrin C increased the expression of superoxide dismutase (SOD) enzymes as well as heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) through the phosphorylated-protein kinase B (p-AKT) and nuclear factor erythroid 2-related factor-2 (Nrf-2) pathways. The anti-inflammatory and anti-oxidant properties of Schisandrin C promoted mitochondrial biogenesis. Conclusions : These results suggest that Schisandrin C may be used as an anti-inflammatory compound to reduce oral inflammation such as pulpitis.

Anti-Inflammatory Effect of Schisandrin C in LPS-Induced Human Dental Pulp Cells

Jyoti Shrestha Takanche,Sang Won Lee(이상원),Yae Jin Kim(김예진),Young Hee Lee(이영희),Jeong Seok Kim(김정석),Ji Eun Kim(김지은),Ho Keun Yi(이호근),Sin Hee Han(한신희) 한국약용작물학회 2016 한국약용작물학회 학술대회논문집 Vol.2016 No.2

Slide Session : OS-END-30 ; Endocrinology : Pattern of Thyroid Dysfunction and Evaluation of Atherosclerotic Cardiovascular Disease Estimator in Patients with Metabolic Syndrome

( Prabin Gyawali ),( Jyoti S Takanche ),( Bijay Krishna Prajapati ),( Rajendra Koju ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Thyroid dysfunction (TD) and metabolic syndrome (Met S) are known risk factors for atherosclerotic cardiovascular disease (ASCVD). TD is risk factor for ASCVD mediated by the effects of thyroid hormones on lipid metabolism and blood pressure hence the components of Met S. Although traditional lipid profile parameters are used to manage ASCVD in patients with Met S, there are no reliable biochemical parameters that can be used in early prediction, diagnosis and primary prevention. Nevertheless, recent studies have recognized serum lipid ratios, atherogenic index of plasma (AIP) and non- HDL Cholesterol (non-HDL-C) as a stronger predictive marker of coronary atherosclerosis and ASCVD events than isolated parameters used independently. Thus, the purpose of this study was to evaluate -the pattern of TD in patients with Met S and - serum lipid ratios, non-HDL cholesterol, and AIP as a predictor of ASCVD in patients with Met S. Methods: Between, October 2012 and March 2014, total of 358 previously diagnosed patients with Met S and 341 healthy controls, who visited diabetes and endocrine clinic at Dhulikhel Hospital, Dhulikhel, Nepal were recruited in the study. The thyroid function test parameters were measured to classify TD and the serum lipid concentrations were measured to calculate the lipid ratios, non-HDL-C and AIP. Results: The overall prevalence of TD in patients with Met S was 31.84 % with high prevalence of subclinical hypothyroidism. Patients with Met S had significantly higher significantly higher lipid ratio`s, non-HDL-C (165.78±48.66 vs 135.21±47.88), and AIP levels (0.810±0.023 vs 0.546±0.014) compared to healthy controls (P < 0.05). Conclusions: Patients with Met S develop sub-clinical hypothyroidism greatly. The measurements of serum lipid ratios, non HDL-C, and AIP level predicts high risk of developing ASCVD in patients with Met S.

Pattern of Thyroid Dysfunction in Patients with Metabolic Syndrome and Its Relationship with Components of Metabolic Syndrome

Prabin Gyawali,Jyoti Shrestha Takanche,Raj Kumar Shrestha,Prem Bhattarai,Kishor Khanal,Prabodh Risal,Rajendra Koju 대한당뇨병학회 2015 Diabetes and Metabolism Journal Vol.39 No.1

Background: Thyroid dysfunction (TD) and metabolic syndrome (MetS) are known risk factors for atherosclerotic cardiovascular disease (ASCVD). TD is risk factor for ASCVD mediated by the effects of thyroid hormones on lipid metabolism and blood pressure hence the components of MetS. It is possible that coexistence of these two disease entities and unrecognized TD in patients with MetS might substantially increase ASCVD risk. Moreover, little is known about the relationship between TD and the components of MetS. Thus, the purpose of this study was to evaluate the pattern of TD in patients with MetS and its relationship with components of the MetS. Methods: A total of 358 previously diagnosed patients with MetS were recruited in the study. The thyroid function test parameters were measured to classify TD at Dhulikhel Hospital-Kathmandu University Hospital, Dhulikhel, Nepal. Statistical analyses were performed using SPSS version 16.0 to evaluate pattern and relationship. Results: The overall prevalence of TD in patients with MetS was 31.84% with high prevalence of subclinical hypothyroidism (29.32%). We found no evidence of a relationship between TD and components of MetS, although there was significant difference in waist circumference between four groups of TD. Conclusion: Patients with MetS had subclinical hypothyroidism greatly. Although there was no evidence of any relationship between thyroid status and all components of MetS, TD should be taken into account when evaluating and treating patients with MetS to reduce the impending risk.