The Effects of Aronia melanocarpa ‘Viking’ Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling
This study aimed to determine the anti-osteoclastogenic effects of extracts from Aronia melanocarpa ‘Viking’ (AM) and identify the underlying mechanisms in vitro. Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW 264.7 cells...
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| Format: | Article |
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MDPI AG
2018-03-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/3/615 |
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| author | Mithun Ghosh In Sook Kim Young Min Lee Seong Min Hong Taek Hwan Lee Ji Hong Lim Trishna Debnath Beong Ou Lim |
| author_facet | Mithun Ghosh In Sook Kim Young Min Lee Seong Min Hong Taek Hwan Lee Ji Hong Lim Trishna Debnath Beong Ou Lim |
| author_sort | Mithun Ghosh |
| collection | DOAJ |
| description | This study aimed to determine the anti-osteoclastogenic effects of extracts from Aronia melanocarpa ‘Viking’ (AM) and identify the underlying mechanisms in vitro. Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW 264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL) were also investigated. RANKL triggers many transcription factors through the activation of mitogen-activated protein kinase (MAPK) and ROS, leading to the induction of osteoclast-specific genes. The extracts significantly suppressed RANKL-induced activation of MAPKs, such as extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38 and consequently led to the downregulation of c-Fos and nuclear factor of activated T cells 1 (NFATc1) protein expression which ultimately suppress the activation of the osteoclast-specific genes, cathepsin K, TRAP, calcitonin receptor and integrin β3. In conclusion, our findings suggest that AM extracts inhibited RANKL-induced osteoclast differentiation by downregulating ROS generation and inactivating JNK/ERK/p38, nuclear factor kappa B (NF-κB)-mediated c-Fos and NFATc1 signaling pathway. |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-12T10:22:35Z |
| publishDate | 2018-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4249c4a1c1f64c35a738db08a22a4a252022-12-22T03:37:04ZengMDPI AGMolecules1420-30492018-03-0123361510.3390/molecules23030615molecules23030615The Effects of Aronia melanocarpa ‘Viking’ Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 SignalingMithun Ghosh0In Sook Kim1Young Min Lee2Seong Min Hong3Taek Hwan Lee4Ji Hong Lim5Trishna Debnath6Beong Ou Lim7Department of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, KoreaDepartment of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, KoreaDepartment of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, KoreaDepartment of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, KoreaDepartment of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, KoreaDepartment of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, KoreaDepartment of Food Science and Biotechnology, Dongguk University-Seoul, Goyang-si, Gyeonggi-do 10326, KoreaDepartment of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, KoreaThis study aimed to determine the anti-osteoclastogenic effects of extracts from Aronia melanocarpa ‘Viking’ (AM) and identify the underlying mechanisms in vitro. Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW 264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL) were also investigated. RANKL triggers many transcription factors through the activation of mitogen-activated protein kinase (MAPK) and ROS, leading to the induction of osteoclast-specific genes. The extracts significantly suppressed RANKL-induced activation of MAPKs, such as extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38 and consequently led to the downregulation of c-Fos and nuclear factor of activated T cells 1 (NFATc1) protein expression which ultimately suppress the activation of the osteoclast-specific genes, cathepsin K, TRAP, calcitonin receptor and integrin β3. In conclusion, our findings suggest that AM extracts inhibited RANKL-induced osteoclast differentiation by downregulating ROS generation and inactivating JNK/ERK/p38, nuclear factor kappa B (NF-κB)-mediated c-Fos and NFATc1 signaling pathway.http://www.mdpi.com/1420-3049/23/3/615osteoclastRANKLphenolROSfree radical |
| spellingShingle | Mithun Ghosh In Sook Kim Young Min Lee Seong Min Hong Taek Hwan Lee Ji Hong Lim Trishna Debnath Beong Ou Lim The Effects of Aronia melanocarpa ‘Viking’ Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling Molecules osteoclast RANKL phenol ROS free radical |
| title | The Effects of Aronia melanocarpa ‘Viking’ Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling |
| title_full | The Effects of Aronia melanocarpa ‘Viking’ Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling |
| title_fullStr | The Effects of Aronia melanocarpa ‘Viking’ Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling |
| title_full_unstemmed | The Effects of Aronia melanocarpa ‘Viking’ Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling |
| title_short | The Effects of Aronia melanocarpa ‘Viking’ Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling |
| title_sort | effects of aronia melanocarpa viking extracts in attenuating rankl induced osteoclastic differentiation by inhibiting ros generation and c fos nfatc1 signaling |
| topic | osteoclast RANKL phenol ROS free radical |
| url | http://www.mdpi.com/1420-3049/23/3/615 |
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