Diallyl disulfide alleviates inflammatory osteolysis by suppressing osteoclastogenesis via NF‐κB–NFATc1 signal pathway

Abstract

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-dependent manner via inhibiting 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 cytokines with LPS stimulation to indirectly mediate osteoclast formation. Consistent with the in vitro results, 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 osteoclastogenesis via NF-κB–NFATc1 signal pathway.

β-Ecdysterone Prevents LPS-Induced Osteoclastogenesis by Regulating NF-κB Pathway in Vitro

“…Studies have demonstrated that LPS can promote osteoclast differentiation by enhancing COX-2 expression and activating RANK, JNK and ERK1/2 pathways [33]. Besides, LPS can also accelerate osteoclast differentiation by activating NF-κB-NFATc1 signal pathway [34]. In this study, we found that LPS can increase the expressions of TRAPpositive cells, osteoclasts-related genes and pro-in ammatory cytokines in RAW264.7 cells.…”

Epothilone B prevents lipopolysaccharide-induced inflammatory osteolysis through suppressing osteoclastogenesis via STAT3 signaling pathway

“…STAT3 signaling pathway was regulated by the activation of PI3K-Akt in cell proliferation and cell differentiation [12]. A recent study reported that LPS induced osteoclastogenesis via the activation of NF-κB-NFATc1 and STAT3 signaling pathways, which were significantly blocked by treatment with diallyl disulfide [13].…”

Curcumin has immunomodulatory effects on RANKL‐stimulated osteoclastogenesis in vitro and titanium nanoparticle‐induced bone loss in vivo

“…The results showed that curcumin markedly attenuated the formation Because bone resorption capacity directly reflects the function of osteoclasts, hydroxyapatite-coated 24-well plates were used in this study. 22,23 After incubation in osteoclast induction medium for 4 days, the medium was replaced with medium containing 0, 1.25, 5 or 20 μmol/L curcumin, and the cells were cultured for an additional 2 days. The area of bone resorption significantly increased without curcumin intervention in the control group; however, the formation of osteoclastic resorption pits decreased as the curcumin concentration increased (Figure 2B,D).…”

“…Scale bar = 100 μm of F-actin rings as the curcumin concentration increased, whereas numerous well-organized F-actin rings were observed without curcumin treatment(Figure 2A,C).Because bone resorption capacity directly reflects the function of osteoclasts, hydroxyapatite-coated 24-well plates were used in this study 22,23. A, Chemical structure of curcumin (MW = 368.37).…”