Strontium inhibits titanium particle-induced osteoclast activation and chronic inflammation via suppression of NF-κB pathway

Abstract

Wear-particle-induced chronic inflammation and osteoclastogenesis have been identified as critical factors of aseptic loosening. Although strontium is known to be involved in osteoclast differentiation, its effect on particle-induced inflammatory osteolysis remains unclear. In this study, we investigate the potential impact and underling mechanism of strontium on particle-induced osteoclast activation and chronic inflammation in vivo and in vitro. As expected, strontium significantly inhibited titanium particle-induced inflammatory infiltration and prevented bone loss in a murine calvarial osteolysis model. Interestingly, the number of mature osteoclasts decreased after treatment with strontium in vivo, suggesting osteoclast formation might be inhibited by strontium. Additionally, low receptor activator of nuclear factor-κB ligand (RANKL), tumor necrosis factor-α, interleukin-1β, interleukin-6 and p65 immunochemistry staining were observed in strontium-treatment groups. In vitro, strontium obviously decreased osteoclast formation, osteoclastogenesis-related gene expression, osteoclastic bone resorption and pro-inflammatory cytokine expression in bone-marrow-derived macrophages in a dose-dependent manner. Furthermore, we demonstrated that strontium impaired osteoclastogenesis by blocking RANKL-induced activation of NF-κB pathway. In conclusion, our study demonstrated that strontium can significantly inhibit particle-induced osteoclast activation and inflammatory bone loss by disturbing the NF-κB pathway, and is an effective therapeutic agent for the treatment of wear particle-induced aseptic loosening.

Strontium ion attenuates lipopolysaccharide‐stimulated proinflammatory cytokine expression and lipopolysaccharide‐inhibited early osteogenic differentiation of human periodontal ligament cells

“…The presence of Sr 2+ ‐substituted biphasic calcium phosphate particles decreased the production of TNFα, IL‐6 and IL‐8 in LPS‐stimulated monocytes. Additionally, a new animal study suggested that Sr 2+ significantly inhibited titanium particle‐induced inflammatory infiltration and bone loss via suppression of the nuclear factor‐kappaB pathway in a murine calvarial osteolysis model . We thus hypothesized that Sr 2+ could induce an anti‐inflammatory and an anti‐osteoclastogenic effect, implying it has a therapeutic effect for periodontitis.…”

“…Additionally, a new animal study suggested that Sr 2+ significantly inhibited titanium particle-induced inflammatory infiltration and bone loss via suppression of the nuclear factor-kappaB pathway in a murine calvarial osteolysis model. 28 We thus hypothesized that Sr 2+ could induce an anti-inflammatory and an anti-osteoclastogenic effect, implying it has a therapeutic effect for periodontitis. These findings are essential for the application of Sr 2+ in periodontitis and periodontal regeneration.…”

Cannabinoid Receptor 2 Agonist Prevents Local and Systemic Inflammatory Bone Destruction in Rheumatoid Arthritis

“…The RAW264.7 cells were plated in 24-well plates in triplicate and transfected with an NF-kB and NFATc1 luciferase reporter construct, as described. (33,35) Briefly, the cells were cultured for 24 hours and then stimulated with RANKL (50 ng/mL), JWH133 (1mM), or SR144528 (100nM) for 8 hours. After that, the cell lysates were isolated and luciferase activity was measured using a dual-luciferase reporter assay system.…”

Nanosized Alumina Particle and Proteasome Inhibitor Bortezomib Prevented inflammation and Osteolysis Induced by Titanium Particle via Autophagy and NF-κB Signaling

“…We found that co-cultured Ti with Al-NPs could slightly inhibit the degradation of the NF-kB inhibitory subunit IκBα and suppressed the activation NF-kB. What' more, it lightly reduced the generation of inflammatory mediators 41,51 . And with our further study, we found that the Al signifiganct prevented the IL-1β expression ( # p < 0.05) via attenuating the NF-kB signaling activator β-TRCP and reducing the expression of Casepase-3 ( Fig.…”

“…Bortezomib (BTZ), which is one of the reversible proteasome inhibitors, has been shown to be a potent inhibitor of NF-κB 38,39 . Bortezomib could block the nuclear transport of NF-kappaB, mainly by inhibiting the chymotryptic activity of polyubiquitinated protein degradation in 26S proteasome 30,[40][41][42][43] . Bortezomib at the first has been approved by FDA as a drug for the therapy of tumor, but it is now also considered as a remedy for non-tumorous diseases such as inflammation diseases [44][45][46] .…”