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The Effects of Aronia melanocarpa 'Viking' Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling.
Molecules. 2018 Mar 08; 23(3)M

Abstract

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.

Authors+Show Affiliations

Department of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, Korea. mithunghoshmg@gmail.com.Department of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, Korea. inskim@sookmyung.ac.kr.Department of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, Korea. waz12345@naver.com.Department of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, Korea. hongsm0107@kku.ac.kr.Department of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, Korea. thlee@ag-health.com. Ahn-Gook Health, LTD, Seoul 07445, Korea. thlee@ag-health.com.Department of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, Korea. jhlim@kku.ac.kr.Department of Food Science and Biotechnology, Dongguk University-Seoul, Goyang-si, Gyeonggi-do 10326, Korea. trishna_rahul@yahoo.com.Department of Applied Life Science, College of Biomedical & Health Science, Konkuk University, Chungju-si, Chungcheongbuk-do 27478, Korea. beongou@kku.ac.kr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29518052

Citation

Ghosh, Mithun, et al. "The Effects of Aronia Melanocarpa 'Viking' Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation By Inhibiting ROS Generation and c-FOS/NFATc1 Signaling." Molecules (Basel, Switzerland), vol. 23, no. 3, 2018.
Ghosh M, Kim IS, Lee YM, et al. The Effects of Aronia melanocarpa 'Viking' Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling. Molecules. 2018;23(3).
Ghosh, M., Kim, I. S., Lee, Y. M., Hong, S. M., Lee, T. H., Lim, J. H., Debnath, T., & Lim, B. O. (2018). The Effects of Aronia melanocarpa 'Viking' Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling. Molecules (Basel, Switzerland), 23(3). https://doi.org/10.3390/molecules23030615
Ghosh M, et al. The Effects of Aronia Melanocarpa 'Viking' Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation By Inhibiting ROS Generation and c-FOS/NFATc1 Signaling. Molecules. 2018 Mar 8;23(3) PubMed PMID: 29518052.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Effects of Aronia melanocarpa 'Viking' Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling. AU - Ghosh,Mithun, AU - Kim,In Sook, AU - Lee,Young Min, AU - Hong,Seong Min, AU - Lee,Taek Hwan, AU - Lim,Ji Hong, AU - Debnath,Trishna, AU - Lim,Beong Ou, Y1 - 2018/03/08/ PY - 2018/01/26/received PY - 2018/02/26/revised PY - 2018/03/06/accepted PY - 2018/3/9/entrez PY - 2018/3/9/pubmed PY - 2018/8/28/medline KW - RANKL KW - ROS KW - free radical KW - osteoclast KW - phenol JF - Molecules (Basel, Switzerland) JO - Molecules VL - 23 IS - 3 N2 - 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. SN - 1420-3049 UR - https://www.unboundmedicine.com/medline/citation/29518052/The_Effects_of_Aronia_melanocarpa_'Viking'_Extracts_in_Attenuating_RANKL_Induced_Osteoclastic_Differentiation_by_Inhibiting_ROS_Generation_and_c_FOS/NFATc1_Signaling_ L2 - http://www.mdpi.com/resolver?pii=molecules23030615 DB - PRIME DP - Unbound Medicine ER -