Diallyl disulfide alleviates inflammatory osteolysis by suppressing osteoclastogenesis via NF-κB-NFATc1 signal pathway. - GreenMedInfo Summary
Diallyl disulfide alleviates inflammatory osteolysis by suppressing osteoclastogenesisNF-κB-NFATc1 signal pathway.
FASEB J. 2019 06 ;33(6):7261-7273. Epub 2019 Mar 11. PMID: 30857415
Jing Yang
Skeletal homeostasis is closely effectuated by the regulation of bone formation and bone resorption. Osteoclasts are multinuclear giant cells responsible for bone resorption. Overactivated osteoclasts and excessive bone resorption result in various lytic bone diseases, such as osteoporosis, osteoarthritis, periprosthetic infection, and inflammatory aseptic loosening of orthopedic implants. In consideration of the severe side effects caused by the currently available drugs, exploitation of novel drugs has gradually attracted attention. Because of its anti-inflammatory, antioxidant, and antitumor capacities, diallyl disulfide (DADS), a major oil-soluble organosulfur ingredient compound derived from garlic, has been widely researched. However, the effects of DADS on osteoclasts and lytic bone diseases are still unknown. In this study, we investigated the effects of DADS on receptor activator of NF-κB ligand (RANKL)- and LPS-mediated osteoclastogenesis, LPS-stimulated proinflammatory cytokines related to osteoclasts, and LPS-induced inflammatory osteolysis. The results showed that DADS significantly inhibited RANKL-mediated osteoclast formation, fusion, and bone resorption in a dose-dependentmannerinhibiting the NF-κB and signal transducer and activator of transcription 3 signaling and restraining the interaction of NF-κB p65 with nuclear factor of activated T cells cytoplasmic 1. Furthermore, DADS also markedly suppressed LPS-induced osteoclastogenesis and reduced the production of proinflammatory cytokineswith LPS stimulation to indirectly mediate osteoclast formation. Consistent with theresults, DADS prevented the LPS-induced severe bone loss by blocking the osteoclastogenesis. All of the results indicate that DADS may be a potential and exploitable drug used for preventing and impeding osteolytic lesions.-Yang, J., Tang, R., Yi, J., Chen, Y., Li, X., Yu, T., Fei, J. Diallyl disulfide alleviates inflammatory osteolysis by suppressing osteoclastogenesisNF-κB-NFATc1 signal pathway.