Phytol Suppresses Osteoclast Differentiation and Oxidative Stress through Nrf2/HO-1 Regulation in RANKL-Induced RAW264.7 Cells
Osteoporosis is a systemic skeletal disorder where osteoclasts are prevalent among osteoblasts. Oxidative stress is one of the main causes of osteoporosis, and nuclear factor erythroid-2-related factor 2 (Nrf2) is the master regulator of antioxidant responses. Phytol, a diterpene isolated from <i...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/22/3596 |
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| author | Eun-Nam Kim Nguyen Minh Trang Heesun Kang Ki Hyun Kim Gil-Saeng Jeong |
| author_facet | Eun-Nam Kim Nguyen Minh Trang Heesun Kang Ki Hyun Kim Gil-Saeng Jeong |
| author_sort | Eun-Nam Kim |
| collection | DOAJ |
| description | Osteoporosis is a systemic skeletal disorder where osteoclasts are prevalent among osteoblasts. Oxidative stress is one of the main causes of osteoporosis, and nuclear factor erythroid-2-related factor 2 (Nrf2) is the master regulator of antioxidant responses. Phytol, a diterpene isolated from <i>Stevia rebaudiana</i> leaves, has many biological effects, including antimicrobial, antioxidant, and anti-inflammatory effects. This study investigated the crosstalk between Nrf2 and osteoclast differentiation in the presence of phytol. Phytol inhibited osteoclast differentiation through TRAP-positive and F-actin formation. The expression of anti-nuclear factor of activated T cells-c1 (NFATc1) and c-Fos was suppressed by phytol, as shown using Western blot and RT-PCR analysis. Phytol inhibited oxidative stress by suppressing reactive oxidant species (ROS) accumulation while recovering antioxidant enzymes, including superoxide dismutase and catalase. Additionally, phytol ameliorated osteoclast-specific differentiation, function, and oxidative stress through Nrf2 regulation by siRNA transfection. In conclusion, these data demonstrate the inhibitory effect of phytol on osteoclast differentiation through Nrf2 regulation, suggesting its potential use in oxidative stress-related osteoporosis and bone diseases. |
| first_indexed | 2024-03-09T18:25:11Z |
| format | Article |
| id | doaj.art-2edcf28dcebe4ba8b54c5b939f86458b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T18:25:11Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2edcf28dcebe4ba8b54c5b939f86458b2023-11-24T07:58:02ZengMDPI AGCells2073-44092022-11-011122359610.3390/cells11223596Phytol Suppresses Osteoclast Differentiation and Oxidative Stress through Nrf2/HO-1 Regulation in RANKL-Induced RAW264.7 CellsEun-Nam Kim0Nguyen Minh Trang1Heesun Kang2Ki Hyun Kim3Gil-Saeng Jeong4College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaOsteoporosis is a systemic skeletal disorder where osteoclasts are prevalent among osteoblasts. Oxidative stress is one of the main causes of osteoporosis, and nuclear factor erythroid-2-related factor 2 (Nrf2) is the master regulator of antioxidant responses. Phytol, a diterpene isolated from <i>Stevia rebaudiana</i> leaves, has many biological effects, including antimicrobial, antioxidant, and anti-inflammatory effects. This study investigated the crosstalk between Nrf2 and osteoclast differentiation in the presence of phytol. Phytol inhibited osteoclast differentiation through TRAP-positive and F-actin formation. The expression of anti-nuclear factor of activated T cells-c1 (NFATc1) and c-Fos was suppressed by phytol, as shown using Western blot and RT-PCR analysis. Phytol inhibited oxidative stress by suppressing reactive oxidant species (ROS) accumulation while recovering antioxidant enzymes, including superoxide dismutase and catalase. Additionally, phytol ameliorated osteoclast-specific differentiation, function, and oxidative stress through Nrf2 regulation by siRNA transfection. In conclusion, these data demonstrate the inhibitory effect of phytol on osteoclast differentiation through Nrf2 regulation, suggesting its potential use in oxidative stress-related osteoporosis and bone diseases.https://www.mdpi.com/2073-4409/11/22/3596phytolNrf2oxidative stresssiRNAosteoclast |
| spellingShingle | Eun-Nam Kim Nguyen Minh Trang Heesun Kang Ki Hyun Kim Gil-Saeng Jeong Phytol Suppresses Osteoclast Differentiation and Oxidative Stress through Nrf2/HO-1 Regulation in RANKL-Induced RAW264.7 Cells Cells phytol Nrf2 oxidative stress siRNA osteoclast |
| title | Phytol Suppresses Osteoclast Differentiation and Oxidative Stress through Nrf2/HO-1 Regulation in RANKL-Induced RAW264.7 Cells |
| title_full | Phytol Suppresses Osteoclast Differentiation and Oxidative Stress through Nrf2/HO-1 Regulation in RANKL-Induced RAW264.7 Cells |
| title_fullStr | Phytol Suppresses Osteoclast Differentiation and Oxidative Stress through Nrf2/HO-1 Regulation in RANKL-Induced RAW264.7 Cells |
| title_full_unstemmed | Phytol Suppresses Osteoclast Differentiation and Oxidative Stress through Nrf2/HO-1 Regulation in RANKL-Induced RAW264.7 Cells |
| title_short | Phytol Suppresses Osteoclast Differentiation and Oxidative Stress through Nrf2/HO-1 Regulation in RANKL-Induced RAW264.7 Cells |
| title_sort | phytol suppresses osteoclast differentiation and oxidative stress through nrf2 ho 1 regulation in rankl induced raw264 7 cells |
| topic | phytol Nrf2 oxidative stress siRNA osteoclast |
| url | https://www.mdpi.com/2073-4409/11/22/3596 |
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