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Article ; Online: MiSurv: an Integrative Web Cloud Platform for User-Friendly Microbiome Data Analysis with Survival Responses.

Gu, Won / Koh, Hyunwook / Jang, Hyojung / Lee, Byungho / Kang, Byungkon

2023 Volume 11, Issue 3, Page(s) e0505922

Abstract: Investigators have studied the treatment effects on human health or disease, the treatment effects on human microbiome, and the roles of the microbiome on human health or disease. Especially, in a clinical trial, investigators commonly trace disease ... ...

Abstract	Investigators have studied the treatment effects on human health or disease, the treatment effects on human microbiome, and the roles of the microbiome on human health or disease. Especially, in a clinical trial, investigators commonly trace disease status over a lengthy period to survey the sequential disease progression for different treatment groups (e.g., treatment versus placebo, new treatment versus old treatment). Hence, disease responses are often available in the form of survival (i.e., time-to-event) responses stratified by treatment groups. While the recent web cloud platforms have enabled user-friendly microbiome data processing and analytics, there is currently no web cloud platform to analyze microbiome data with survival responses. Therefore, we introduce here an integrative web cloud platform, called MiSurv, for comprehensive microbiome data analysis with survival responses.
MeSH term(s)	Humans ; Cloud Computing ; Diabetes Mellitus, Type 1 ; Gastrointestinal Microbiome ; Microbiota
Language	English
Publishing date	2023-04-11
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.05059-22
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Article ; Online: Policosanol Stimulates Osteoblast Differentiation via Adenosine Monophosphate-Activated Protein Kinase-Mediated Expression of Insulin-Induced Genes 1 and 2.

Kim, Kyeong-Min / Lim, Young-Ju / Jang, Won-Gu

Cells

2023 Volume 12, Issue 14

Abstract: Policosanol is known as a hypocholesterolemic compound and is derived from plants such as sugar cane and corn. Policosanol can lower blood pressure or inhibit adipogenesis, but its effect on osteogenic differentiation and the molecular mechanism is ... ...

Abstract	Policosanol is known as a hypocholesterolemic compound and is derived from plants such as sugar cane and corn. Policosanol can lower blood pressure or inhibit adipogenesis, but its effect on osteogenic differentiation and the molecular mechanism is unclear. This study aims to investigate the effect of policosanol on osteogenic differentiation in MC3T3-E1 cells and zebrafish models. Administration of policosanol into MC3T3-E1 induced the expression of the osteogenic genes such as distal-less homeobox 5 (Dlx5) and runt-related transcription factor 2 (Runx2). Alkaline phosphatase activity and extracellular mineralization also increased. Policosanol promoted activation of adenosine monophosphate-activated protein kinase (AMPK) and insulin-induced genes (INSIGs) expression and regulation of INSIGs modulated osteoblast differentiation. AMPK activation through transfection of the constitutively active form of AMPK (CA-AMPK) increased INSIGs expression, whereas policosanol-induced INSIGs expression was suppressed by inhibitor of AMPK (Com. C). Furthermore, the osteogenic effects of policosanol were verified in zebrafish. Amputated caudal fin rays were regenerated by policosanol treatment. Taken together, these results show that policosanol increases osteogenic differentiation and contributes to fin regeneration in zebrafish via AMPK-mediated INSIGs expression, suggesting that policosanol has potential as an osteogenic agent.
MeSH term(s)	Animals ; Osteogenesis ; Zebrafish/metabolism ; AMP-Activated Protein Kinases/metabolism ; Osteoblasts/metabolism ; Cell Differentiation ; Insulins/metabolism ; Insulins/pharmacology
Chemical Substances	policosanol (142583-61-7) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Insulins
Language	English
Publishing date	2023-07-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12141863
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Article ; Online: Integrative web cloud computing and analytics using MiPair for design-based comparative analysis with paired microbiome data.

Jang, Hyojung / Koh, Hyunwook / Gu, Won / Kang, Byungkon

Scientific reports

2022 Volume 12, Issue 1, Page(s) 20465

Abstract: Pairing (or blocking) is a design technique that is widely used in comparative microbiome studies to efficiently control for the effects of potential confounders (e.g., genetic, environmental, or behavioral factors). Some typical paired (block) designs ... ...

Abstract	Pairing (or blocking) is a design technique that is widely used in comparative microbiome studies to efficiently control for the effects of potential confounders (e.g., genetic, environmental, or behavioral factors). Some typical paired (block) designs for human microbiome studies are repeated measures designs that profile each subject's microbiome twice (or more than twice) (1) for pre and post treatments to see the effects of a treatment on microbiome, or (2) for different organs of the body (e.g., gut, mouth, skin) to see the disparity in microbiome between (or across) body sites. Researchers have developed a sheer number of web-based tools for user-friendly microbiome data processing and analytics, though there is no web-based tool currently available for such paired microbiome studies. In this paper, we thus introduce an integrative web-based tool, named MiPair, for design-based comparative analysis with paired microbiome data. MiPair is a user-friendly web cloud service that is built with step-by-step data processing and analytic procedures for comparative analysis between (or across) groups or between baseline and other groups. MiPair employs parametric and non-parametric tests for complete or incomplete block designs to perform comparative analyses with respect to microbial ecology (alpha- and beta-diversity) and taxonomy (e.g., phylum, class, order, family, genus, species). We demonstrate its usage through an example clinical trial on the effects of antibiotics on gut microbiome. MiPair is an open-source software that can be run on our web server ( http://mipair.micloud.kr ) or on user's computer ( https://github.com/yj7599/mipairgit ).
MeSH term(s)	Humans ; Cloud Computing ; Microbiota ; Gastrointestinal Microbiome ; Mouth ; Skin
Language	English
Publishing date	2022-11-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-25093-6
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Article ; Online: NXNL1 negatively regulates osteoblast differentiation via GDF15-induced PP2A Cα dependent manner in MC3T3-E1 cells.

Kim, Kyeong-Min / Jang, Won-Gu

BioFactors (Oxford, England)

2021 Volume 48, Issue 1, Page(s) 239–248

Abstract: Controlling the level of intracellular reactive oxygen species (ROS) is important for the survival and differentiation of osteoblasts. Intracellular ROS levels are controlled by antioxidant enzymes that modulate the redox state of the cell. Nucleoredoxin- ...

Abstract	Controlling the level of intracellular reactive oxygen species (ROS) is important for the survival and differentiation of osteoblasts. Intracellular ROS levels are controlled by antioxidant enzymes that modulate the redox state of the cell. Nucleoredoxin-like 1 (NXNL1) is an antioxidant enzyme that increases the viability of rod and cone cells by protecting them from oxidative stress, and is a potential pharmacological target for the treatment of retinitis pigmentosa. The present study investigated the role of NXNL on osteoblast differentiation of MC3T3-E1 preosteoblast cells. Results from qPCR experiments demonstrated that growth differentiation factor 15 (GDF15) increased NXNL1 expression, and that GDF15-induced NXNL1 decreased the expression of osteogenic genes such as distal-less homeobox 5 (Dlx5) and Runt-related transcription factor 2. Furthermore, NXNL1 also inhibits bone morphogenetic protein 2-induced phosphorylation of Smad1/5/9 and alkaline phosphatase activity. The inhibitory effects of NXNL1 on osteoblast differentiation were mediated by protein phosphatase 2A Cα (PP2A Cα). The expression of PP2A Cα was regulated by GDF15, and overexpression of PP2A Cα increased the expression of NXNL1. Taken together, our results demonstrate that NXNL1 inhibits osteoblast differentiation of MC3T3-E1 due to GDF15-induced expression of PP2A Cα.
MeSH term(s)	Animals ; Cell Differentiation ; Cell Line ; Growth Differentiation Factor 15/genetics ; Mice ; Osteoblasts/cytology ; Osteogenesis ; Protein Phosphatase 2/genetics ; Thioredoxins/genetics
Chemical Substances	Gdf15 protein, mouse ; Growth Differentiation Factor 15 ; Thioredoxins (52500-60-4) ; PPP2CA protein, mouse (EC 3.1.3.16) ; Protein Phosphatase 2 (EC 3.1.3.16)
Language	English
Publishing date	2021-12-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	59230-4
ISSN	1872-8081 ; 0951-6433
ISSN (online)	1872-8081
ISSN	0951-6433
DOI	10.1002/biof.1817
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Article ; Online: Cip2A modulates osteogenic differentiation via the ERK-Runx2 pathway in MG63 cells.

Son, Hyo-Eun / Jang, Won-Gu

BioFactors (Oxford, England)

2021 Volume 47, Issue 4, Page(s) 658–664

Abstract: Cancerous inhibitor of protein phosphatase 2A (Cip2A) is an oncoprotein that promotes the development of several types of cancer. However, its molecular function in osteoblast differentiation remains unclear. In this study, we found that Cip2A was ... ...

Abstract	Cancerous inhibitor of protein phosphatase 2A (Cip2A) is an oncoprotein that promotes the development of several types of cancer. However, its molecular function in osteoblast differentiation remains unclear. In this study, we found that Cip2A was upregulated under osteogenic conditions in MG63 cells. Besides, overexpression of Cip2A significantly increased the expression of Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP). Inversely, the knockdown of Cip2A in MG63 cells suppressed osteoblast differentiation. Cip2A expression during osteogenic differentiation was mediated by extracellular signal-regulated kinase (ERK) activation. Taken together, our results suggest that Cip2A plays important role in regulating osteoblast differentiation by inducing ERK phosphorylation in MG63 cells.
MeSH term(s)	Alkaline Phosphatase/genetics ; Alkaline Phosphatase/metabolism ; Autoantigens/genetics ; Autoantigens/metabolism ; Bone Morphogenetic Protein 2/pharmacology ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Core Binding Factor Alpha 1 Subunit/genetics ; Core Binding Factor Alpha 1 Subunit/metabolism ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Membrane Proteins/antagonists & inhibitors ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mitogen-Activated Protein Kinase 1/genetics ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/genetics ; Mitogen-Activated Protein Kinase 3/metabolism ; Osteoblasts/drug effects ; Osteoblasts/metabolism ; Osteoblasts/pathology ; Osteogenesis/drug effects ; Osteogenesis/genetics ; Phosphorylation/drug effects ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases/genetics ; p38 Mitogen-Activated Protein Kinases/metabolism
Chemical Substances	Autoantigens ; BMP2 protein, human ; Bone Morphogenetic Protein 2 ; CIP2A protein, human ; Core Binding Factor Alpha 1 Subunit ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; RNA, Small Interfering ; RUNX2 protein, human ; MAPK1 protein, human (EC 2.7.11.24) ; MAPK3 protein, human (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 1 (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Alkaline Phosphatase (EC 3.1.3.1)
Language	English
Publishing date	2021-06-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	59230-4
ISSN	1872-8081 ; 0951-6433
ISSN (online)	1872-8081
ISSN	0951-6433
DOI	10.1002/biof.1760
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Article ; Online: Topiramate promotes osteogenic differentiation through AMPK-dependent phosphorylation of Smad1/5/9.

Kim, Kyeong-Min / Son, Hyo-Eun / Lim, Young-Ju / Jang, Won-Gu

Acta histochemica

2023 Volume 125, Issue 7, Page(s) 152095

Abstract: Topiramate [2,3:4,5-bis-o-(1-methylethylidene) β-D-fructo-pyranose sulfamate; TPM] is one of the most used new-generation antiepileptic drugs. It has been reported to regulate the differentiation of human bone cells. However, the molecular mechanism of ... ...

Abstract	Topiramate [2,3:4,5-bis-o-(1-methylethylidene) β-D-fructo-pyranose sulfamate; TPM] is one of the most used new-generation antiepileptic drugs. It has been reported to regulate the differentiation of human bone cells. However, the molecular mechanism of TPM in osteoblast differentiation is not fully elucidated. In the present study, we examined the effect of TPM on osteogenic differentiation of C3H10T1/2, MC3T3-E1, primary mouse calvarial cells, and primary bone marrow stem cells (BMSCs). Primary cells were isolated from mice calvaria and bone marrow respectively. Expression of the osteogenic gene was determined by RT-PCR. The osteogenic protein levels were measured by Western blot analysis. Alkaline phosphatase (ALP) staining experiment was performed to evaluate ALP activity. Alizarin red s (ARS) staining was performed to measure zebrafish caudal fin regeneration. Treatment of TPM up-regulated the osteogenic genes including distal-less homeobox 5 (Dlx5) and runt-related transcription factor 2 (Runx2). In addition, TPM also increased the Dlx5 and Runx2 protein levels, Smad1/5/9 phosphorylation, and alkaline phosphatase (ALP) activity. Furthermore, TPM activated AMPK, and inhibition of AMPK decreased TPM-induced osteogenic differentiation. In the zebrafish model, osteogenic effect of TPM was identified. TPM was increased amputated caudal fin rays of zebrafish. These results demonstrate that TPM enhances osteogenic differentiation via AMPK-mediated Smad1/5/9 phosphorylation.
Language	English
Publishing date	2023-09-25
Publishing country	Germany
Document type	Journal Article
ZDB-ID	77-2
ISSN	1618-0372 ; 0065-1281
ISSN (online)	1618-0372
ISSN	0065-1281
DOI	10.1016/j.acthis.2023.152095
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Article ; Online: Zingerone stimulates osteoblast differentiation by increasing Smad1/5/9-mediated HO-1 expression in MC3T3-E1 cells and primary mouse calvarial cells.

Kim, A-Rang / Lim, Young-Ju / Jang, Won-Gu

Clinical and experimental pharmacology & physiology

2022 Volume 49, Issue 10, Page(s) 1050–1058

Abstract: Zingerone is a non-volatile compound found mainly in dried ginger. Zingerone increases the expression of osteogenic markers and has antioxidant effects. A previous study showed that zingerone accelerated osteoblast differentiation by suppressing the ... ...

Abstract	Zingerone is a non-volatile compound found mainly in dried ginger. Zingerone increases the expression of osteogenic markers and has antioxidant effects. A previous study showed that zingerone accelerated osteoblast differentiation by suppressing the expression of Smad7, a member of the inhibitory Smad (I-Smad) family. However, it is not known if zingerone can induce osteoblast differentiation by regulating Smad1/5/9, a member of the receptor-regulated Smad (R-Smad) family. In addition, osteoblast differentiation induced by Smad1/5/9 mediated increases in the expression of heme oxygenase 1 (HO-1) has not been reported. This study investigated the effects of zingerone on osteoblast differentiation and confirmed the relationship between Smad1/5/9 and HO-1. Zingerone increased the expression of osteogenic genes including runt-related transcription factor 2 (Runx2), distal-less homeobox (Dlx5) and osteocalcin (OC) and also promoted Smad1/5/9 phosphorylation. Interestingly, HO-1 expression was also elevated by zingerone, and an inhibitor of HO-1 (Sn[IV] protoporphyrin IX dichloride [SnPP]) suppressed the zingerone-induced increase in HO-1 expression and expression of osteogenic marker genes such as Dlx5, Runx2 and OC. Protein phosphatase 2A Cα (PP2A Cα, an inhibitor of Smad1/5/9) suppressed the zingerone-induced increase in HO-1 expression and expression of osteogenic marker genes. The zingerone-induced increase in HO-1 luciferase activity was suppressed by PP2A Cα. Taken together; our data demonstrate that zingerone promotes osteoblast differentiation by increasing Smad1/5/9 mediated HO-1 expression.
MeSH term(s)	Animals ; Bone Morphogenetic Protein 2/metabolism ; Cell Differentiation ; Core Binding Factor Alpha 1 Subunit/genetics ; Core Binding Factor Alpha 1 Subunit/metabolism ; Core Binding Factor Alpha 1 Subunit/pharmacology ; Guaiacol/analogs & derivatives ; Heme Oxygenase-1/genetics ; Heme Oxygenase-1/metabolism ; Mice ; Osteoblasts ; Osteocalcin ; Osteogenesis ; Protein Phosphatase 2/genetics ; Protein Phosphatase 2/metabolism ; Smad1 Protein/metabolism ; Transcription Factors/metabolism
Chemical Substances	Bone Morphogenetic Protein 2 ; Core Binding Factor Alpha 1 Subunit ; Smad1 Protein ; Smad1 protein, mouse ; Transcription Factors ; Osteocalcin (104982-03-8) ; zingerone (4MMW850892) ; Guaiacol (6JKA7MAH9C) ; Heme Oxygenase-1 (EC 1.14.14.18) ; Protein Phosphatase 2 (EC 3.1.3.16)
Language	English
Publishing date	2022-07-19
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	189277-0
ISSN	1440-1681 ; 0305-1870 ; 0143-9294
ISSN (online)	1440-1681
ISSN	0305-1870 ; 0143-9294
DOI	10.1111/1440-1681.13681
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Article ; Online: Pharmacokinetic Comparison Between a Fixed-Dose Combination of Atorvastatin/Omega-3-Acid Ethyl Esters and the Corresponding Loose Combination in Healthy Korean Male Subjects.

Khwarg, Juyoung / Lee, Soyoung / Jang, In-Jin / Kang, Won-Ho / Lee, Hye Jung / Kim, Kyu Yeon / Jeong, Ki-Sun / Won, Chongho / Choi, Youn Woong / Ha, Dae Chul / Jung, RaeHoon / Han, Min-Gu / Jung, Won Tae / Nam, Kyu-Yeol / Kim, YeSeul / Yu, Kyung-Sang / Oh, Jaeseong

Drug design, development and therapy

2024 Volume 18, Page(s) 395–406

Abstract: Purpose: Statins are widely used in combination with omega-3 fatty acids for the treatment of patients with dyslipidemia. The aim of this study was to compare the pharmacokinetic (PK) profiles of atorvastatin and omega-3-acid ethyl esters between fixed- ... ...

Abstract	Purpose: Statins are widely used in combination with omega-3 fatty acids for the treatment of patients with dyslipidemia. The aim of this study was to compare the pharmacokinetic (PK) profiles of atorvastatin and omega-3-acid ethyl esters between fixed-dose combination (FDC) and loose combination in healthy subjects. Methods: A randomized, open-label, single-dose, 2-sequence, 2-treatment, 4-period replicated crossover study was performed. Subjects were randomly assigned to one of the 2 sequences and alternately received four FDC soft capsules of atorvastatin/omega-3-acid ethyl esters (10/1000 mg) or a loose combination of atorvastatin tablets (10 mg × 4) and omega-3-acid ethyl ester soft capsules (1000 mg× 4) for four periods, each period accompanied by a high-fat meal. Serial blood samples were collected for PK analysis of atorvastatin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). PK parameters were calculated by a non-compartmental analysis. The geometric mean ratio (GMR) and its 90% confidence interval (CI) of the FDC to the loose combination were calculated to compare PK parameters. Results: A total of 43 subjects completed the study as planned. The GMR (90% CI) of FDC to loose combination for maximum concentration (C Conclusion: The FDC of atorvastatin and omega-3-acid ethyl esters showed comparable PK characteristics to the corresponding loose combination, offering a convenient therapeutic option for the treatment of dyslipidemia.
MeSH term(s)	Humans ; Male ; Atorvastatin ; Eicosapentaenoic Acid/pharmacokinetics ; Healthy Volunteers ; Cross-Over Studies ; Docosahexaenoic Acids ; Dyslipidemias ; Republic of Korea ; Drug Combinations ; Area Under Curve
Chemical Substances	Atorvastatin (A0JWA85V8F) ; Eicosapentaenoic Acid (AAN7QOV9EA) ; Docosahexaenoic Acids (25167-62-8) ; Drug Combinations
Language	English
Publishing date	2024-02-08
Publishing country	New Zealand
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2451346-5
ISSN	1177-8881 ; 1177-8881
ISSN (online)	1177-8881
ISSN	1177-8881
DOI	10.2147/DDDT.S435885
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Article ; Online: Effects of Rumen-Protected L-Tryptophan Supplementation on Productivity, Physiological Indicators, Blood Profiles, and Heat Shock Protein Gene Expression in Lactating Holstein Cows under Heat Stress Conditions.

Jo, Jang-Hoon / Jalil, Ghassemi Nejad / Kim, Won-Seob / Moon, Jun-Ok / Lee, Sung-Dae / Kwon, Chan-Ho / Lee, Hong-Gu

International journal of molecular sciences

2024 Volume 25, Issue 2

Abstract: In this study, we examined the effects of rumen-protected L-tryptophan supplementation on the productivity and physiological metabolic indicators in lactating Holstein cows under heat stress conditions. The study involved eight early lactating Holstein ... ...

Abstract	In this study, we examined the effects of rumen-protected L-tryptophan supplementation on the productivity and physiological metabolic indicators in lactating Holstein cows under heat stress conditions. The study involved eight early lactating Holstein cows (days in milk = 40 ± 9 days; milk yield 30 ± 1.5 kg/day; parity 1.09 ± 0.05,
MeSH term(s)	Pregnancy ; Female ; Cattle ; Animals ; Lactation ; Heat-Shock Proteins/genetics ; Heat-Shock Proteins/metabolism ; Diet/veterinary ; Tryptophan/pharmacology ; Tryptophan/metabolism ; Rumen ; Leukocytes, Mononuclear ; Milk/metabolism ; Heat-Shock Response/physiology ; Dietary Supplements ; Gene Expression ; Hot Temperature
Chemical Substances	Heat-Shock Proteins ; Tryptophan (8DUH1N11BX)
Language	English
Publishing date	2024-01-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25021217
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Article ; Online: Eucalyptol induces osteoblast differentiation through ERK phosphorylation in vitro and in vivo.

Lee, Do-Won / Kim, Kyeong-Min / Park, Seulki / An, Sang-Hyun / Lim, Young-Ju / Jang, Won-Gu

Journal of molecular medicine (Berlin, Germany)

2023 Volume 101, Issue 9, Page(s) 1083–1095

Abstract: Eucalyptol (EU) is monoterpene oxide that is the main component of the essential oil extracted from aromatic plants such as Eucalyptus globules. EU has therapeutic effects such as antibacterial, anti-inflammatory and antioxidant in chronic diseases ... ...

Abstract	Eucalyptol (EU) is monoterpene oxide that is the main component of the essential oil extracted from aromatic plants such as Eucalyptus globules. EU has therapeutic effects such as antibacterial, anti-inflammatory and antioxidant in chronic diseases including inflammation disorder, respiratory disease, and diabetic disease. However, the effects of EU on osteoblast differentiation and bone diseases such as osteoporosis have not been studied. The present study investigated the effects of EU on osteoblast differentiation and bone formation. EU induces mRNA and protein expression of osteogenic genes in osteoblast cell line MC3T3-E1 and primary calvarial osteoblasts. EU also promoted alkaline phosphatase (ALP) activity and mineralization. Here, the osteoblast differentiation effect of EU is completely reversed by ERK inhibitor. These results demonstrate that osteoblast differentiation effect of EU is mediated by ERK phosphorylation. The efficacy of EU on bone formation was investigated using surgical bone loss-induced animal models. EU dose-dependently promoted bone regeneration in zebrafish caudal fin rays. In the case of ovariectomized mice, EU increased ERK phosphorylation and ameliorated bone loss of femurs. These results indicate that EU ameliorates bone loss by promoting osteoblast differentiation through ERK phosphorylation. We suggest that EU, plant-derived monoterpenoid, may be useful for preventing bone loss. KEY MESSAGES: Eucalyptol (EU) increases osteoblast differentiation in pre-osteoblasts. EU up-regulates the osteogenic genes expression via ERK phosphorylation. EU promotes bone regeneration in partially amputated zebrafish fin rays. Oral administration of EU improves ovariectomy-induced bone loss and increases ERK phosphorylation.
MeSH term(s)	Female ; Mice ; Animals ; Osteogenesis ; Zebrafish ; Eucalyptol/metabolism ; Eucalyptol/pharmacology ; Phosphorylation ; Cell Differentiation ; Osteoblasts/metabolism
Chemical Substances	Eucalyptol (RV6J6604TK)
Language	English
Publishing date	2023-07-20
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1223802-8
ISSN	1432-1440 ; 0946-2716
ISSN (online)	1432-1440
ISSN	0946-2716
DOI	10.1007/s00109-023-02348-x
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