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Please use this identifier to cite or link to this item: http://repository.iitr.ac.in/handle/123456789/1526
Title: A pterostilbene derivative suppresses osteoclastogenesis by regulating RANKL-mediated NFκB and MAPK signaling in RAW264.7 cells
Authors: Nikhil K.
Sharan S.
Roy, Partha
Published in: Pharmacological Reports
Abstract: Background A dysfunctional osteoclast activity is often the cause of bone destructive diseases, such as osteoporosis, periodontitis, erosive arthritis, and cancer. The NF?B ligand (RANKL) has been identified as a major mediator of bone resorption. Agents that suppress RANKL signaling have the potential to inhibit bone resorption or osteoclastogenesis. The present study aimed to determine the effect of a pterostilbene derivative (PTERC-T) for suppressing RANKL or tumor cells-induced osteoclastogenesis in RAW264.7 murine macrophages. Methods Cytotoxicity was measured by MTT assay and inhibitory effect on osteoclastogenesis was analyzed by counting the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and measuring the expression levels of the osteoclast-specific genes. The reactive oxygen species (ROS) generation was detected by FACS. Further, signaling pathways were analyzed by immunofluorescence and immunoblot analyses. Results PTERC-T suppressed the differentiation of monocytes to osteoclasts in a dose and time-dependent manner. The expression of osteoclast marker genes like TRAP, cathepsin K (CTSK), matrix metalloproteinase 9 (MMP9) and transcription factors c-Fos, and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) were also diminished by PTERC-T. PTERC-T scavenged intracellular ROS generation within osteoclast precursors during RANKL-stimulated osteoclastogenesis. Mechanistically, PTERC-T abrogated the phosphorylation of MAPKs (ERK and JNK) and inhibited RANKL-induced activation of NF?B by suppressing I?B? phosphorylation and preventing NF?B/p65 nuclear translocation. Conclusions This study thus identifies PTERC-T as an inhibitor of osteoclast formation and provides evidence for its role in preventing osteoporosis and other bone related disorders. However, further studies are needed to establish its efficacy in vivo. © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.
Citation: Pharmacological Reports (2015), 67(6): 1264-1272
URI: https://doi.org/10.1016/j.pharep.2015.05.009
http://repository.iitr.ac.in/handle/123456789/1526
Issue Date: 2015
Publisher: Elsevier
Keywords: MAPK
NF?B
Osteoclastogenesis
PTERC-T
RANKL
ISSN: 17341140
Author Scopus IDs: 57192281884
55661549600
35509207200
Author Affiliations: Nikhil, K., Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, India
Sharan, S., Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, India
Roy, P., Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, India
Funding Details: This work was supported by research grants from Council for Scientific and Industrial Research and Ministry of Human Resources and Development (MHRD) , Government of India as research fellowships to KN and project assistantship to PR, respectively.
Corresponding Author: Roy, P.; Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology RoorkeeIndia; email: paroyfbs@iitr.ernet.in
Appears in Collections:Journal Publications [BT]

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