A pterostilbene derivative suppresses osteoclastogenesis by regulating RANKL-mediated NFκB and MAPK signaling in RAW264.7 cells

Background a dysfunctional osteoclast activity is often the cause of bone destructive diseases,such as osteoporosis,periodontitis,erosive arthritis,and cancer. the nfκb 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 nfκb by suppressing iκbα phosphorylation and preventing nfκb/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.