Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 68, Issue 22, Pages 6132-6141Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.0c01159
Keywords
tripeptide IRW; osteoclastogenesis; inflammation; NF-kappa B; MAPK
Funding
- Natural Sciences and Engineering Research Council (NSERC) of Canada
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Excessive bone resorption, because of increased osteoclastic activity, is a key underlying cause of osteolytic disorders. Lipopolysaccharide (LPS) is a potent factor to stimulate osteoclastic activity by inducing inflammatory stress. An egg-derived tripeptide IRW (Ile-Arg-Trp) was previously shown to exert anti-inflammatory activity. The overall objective of this study was to investigate the effect of IRW on inhibiting LPS-induced osteoclastogenesis and inflammatory bone resorption in the mouse macrophage RAW 264.7 cells. IRW (25 and 50 mu M) significantly inhibited the LPS-induced osteoclast formation and resorptive activity. Meanwhile, IRW significantly suppressed the LPS-induced expression of TNF-alpha, IL-6, iNOS, COXII, NO, and PGE2. Furthermore, IRW regulated a group of osteoclastogenesis-associated factors (TRAF6, c-Fos, NFATc1, and cathepsin K) because of the inhibition of LPS-activated NF-kappa B and MAPK pathways. In conclusion, our study suggested the ability of IRW to prevent LPS-induced inflammatory bone resorption activity via the inhibition of inflammatory responses and the activation of osteoclastogenesis-associated signaling pathways.
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