Palm Tocotrienol Activates the Wnt3a/β-Catenin Signaling Pathway, Protecting MC3T3-E1 Osteoblasts from Cellular Damage Caused by Dexamethasone and Promoting Bone Formation

<b>Background and aim:</b> Prolonged glucocorticoid (GC) treatment increases oxidative stress, triggers apoptosis of osteoblasts, and contributes to osteoporosis. Tocotrienol, as an antioxidant, could protect the osteoblasts and preserve bone quality under glucocorticoid treatment. From...

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Main Authors: Norfarahin Abdullah Sani, Nur Aqilah Kamaruddin, Ima Nirwana Soelaiman, Kok-Lun Pang, Kok-Yong Chin, Elvy Suhana Mohd Ramli
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/1/243
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author Norfarahin Abdullah Sani
Nur Aqilah Kamaruddin
Ima Nirwana Soelaiman
Kok-Lun Pang
Kok-Yong Chin
Elvy Suhana Mohd Ramli
author_facet Norfarahin Abdullah Sani
Nur Aqilah Kamaruddin
Ima Nirwana Soelaiman
Kok-Lun Pang
Kok-Yong Chin
Elvy Suhana Mohd Ramli
author_sort Norfarahin Abdullah Sani
collection DOAJ
description <b>Background and aim:</b> Prolonged glucocorticoid (GC) treatment increases oxidative stress, triggers apoptosis of osteoblasts, and contributes to osteoporosis. Tocotrienol, as an antioxidant, could protect the osteoblasts and preserve bone quality under glucocorticoid treatment. From this study, we aimed to determine the effects of tocotrienol on MC3T3-E1 murine pre-osteoblastic cells treated with GC. <b>Methods:</b> MC3T3-E1 cells were exposed to dexamethasone (150 µM), with or without palm tocotrienol (PTT; 0.25, 0.5, and 1 µg/mL). Cell viability was measured by the MTS assay. Alizarin Red staining was performed to detect calcium deposits. Cellular alkaline phosphatase activity was measured to evaluate osteogenic activity. The expression of osteoblastic differentiation markers was measured by an enzyme-linked immunoassay. <b>Results</b>: Enhanced matrix mineralization was observed in the cells treated with 0.5 µg/mL PTT, especially on day 18 (<i>p</i> < 0.05). The expression of Wnt3a, β-catenin, collagen 1α1, alkaline phosphatase, osteocalcin, low-density lipoprotein receptor-related protein 6, and runt-related transcription factor-2 were significantly increased in the PTT-treated groups compared to the vehicle control group, especially at 0.5 µg/mL of PTT (<i>p</i> < 0.05) and on day 6 of treatment. <b>Conclusions</b>: PTT maintains the osteogenic activity of the dexamethasone-treated osteoblasts by promoting their differentiation.
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institution Kabale University
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spelling doaj-art-dd373c8b763247639acc440080c903502025-01-24T13:24:31ZengMDPI AGBiomedicines2227-90592025-01-0113124310.3390/biomedicines13010243Palm Tocotrienol Activates the Wnt3a/β-Catenin Signaling Pathway, Protecting MC3T3-E1 Osteoblasts from Cellular Damage Caused by Dexamethasone and Promoting Bone FormationNorfarahin Abdullah Sani0Nur Aqilah Kamaruddin1Ima Nirwana Soelaiman2Kok-Lun Pang3Kok-Yong Chin4Elvy Suhana Mohd Ramli5Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, MalaysiaDepartment of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, MalaysiaDepartment of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, MalaysiaDepartment of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, MalaysiaDepartment of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, MalaysiaDepartment of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia<b>Background and aim:</b> Prolonged glucocorticoid (GC) treatment increases oxidative stress, triggers apoptosis of osteoblasts, and contributes to osteoporosis. Tocotrienol, as an antioxidant, could protect the osteoblasts and preserve bone quality under glucocorticoid treatment. From this study, we aimed to determine the effects of tocotrienol on MC3T3-E1 murine pre-osteoblastic cells treated with GC. <b>Methods:</b> MC3T3-E1 cells were exposed to dexamethasone (150 µM), with or without palm tocotrienol (PTT; 0.25, 0.5, and 1 µg/mL). Cell viability was measured by the MTS assay. Alizarin Red staining was performed to detect calcium deposits. Cellular alkaline phosphatase activity was measured to evaluate osteogenic activity. The expression of osteoblastic differentiation markers was measured by an enzyme-linked immunoassay. <b>Results</b>: Enhanced matrix mineralization was observed in the cells treated with 0.5 µg/mL PTT, especially on day 18 (<i>p</i> < 0.05). The expression of Wnt3a, β-catenin, collagen 1α1, alkaline phosphatase, osteocalcin, low-density lipoprotein receptor-related protein 6, and runt-related transcription factor-2 were significantly increased in the PTT-treated groups compared to the vehicle control group, especially at 0.5 µg/mL of PTT (<i>p</i> < 0.05) and on day 6 of treatment. <b>Conclusions</b>: PTT maintains the osteogenic activity of the dexamethasone-treated osteoblasts by promoting their differentiation.https://www.mdpi.com/2227-9059/13/1/243bonedifferentiationosteoporosistocotrienolvitamin Eglucocorticoids
spellingShingle Norfarahin Abdullah Sani
Nur Aqilah Kamaruddin
Ima Nirwana Soelaiman
Kok-Lun Pang
Kok-Yong Chin
Elvy Suhana Mohd Ramli
Palm Tocotrienol Activates the Wnt3a/β-Catenin Signaling Pathway, Protecting MC3T3-E1 Osteoblasts from Cellular Damage Caused by Dexamethasone and Promoting Bone Formation
Biomedicines
bone
differentiation
osteoporosis
tocotrienol
vitamin E
glucocorticoids
title Palm Tocotrienol Activates the Wnt3a/β-Catenin Signaling Pathway, Protecting MC3T3-E1 Osteoblasts from Cellular Damage Caused by Dexamethasone and Promoting Bone Formation
title_full Palm Tocotrienol Activates the Wnt3a/β-Catenin Signaling Pathway, Protecting MC3T3-E1 Osteoblasts from Cellular Damage Caused by Dexamethasone and Promoting Bone Formation
title_fullStr Palm Tocotrienol Activates the Wnt3a/β-Catenin Signaling Pathway, Protecting MC3T3-E1 Osteoblasts from Cellular Damage Caused by Dexamethasone and Promoting Bone Formation
title_full_unstemmed Palm Tocotrienol Activates the Wnt3a/β-Catenin Signaling Pathway, Protecting MC3T3-E1 Osteoblasts from Cellular Damage Caused by Dexamethasone and Promoting Bone Formation
title_short Palm Tocotrienol Activates the Wnt3a/β-Catenin Signaling Pathway, Protecting MC3T3-E1 Osteoblasts from Cellular Damage Caused by Dexamethasone and Promoting Bone Formation
title_sort palm tocotrienol activates the wnt3a β catenin signaling pathway protecting mc3t3 e1 osteoblasts from cellular damage caused by dexamethasone and promoting bone formation
topic bone
differentiation
osteoporosis
tocotrienol
vitamin E
glucocorticoids
url https://www.mdpi.com/2227-9059/13/1/243
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