Chrysin Protects Against Titanium Particle-Induced Osteolysis by Attenuating Osteoclast Formation and Function by Inhibiting NF-κB and MAPK Signaling

Abstract

Bone homeostasis only exists when the physical function of osteoblast and osteoclast stays in the balance between bone formation and resorption. Bone resorption occurs when the two processes are uncoupled, shifting the balance in favour of bone resorption. Excessive activation of osteoclasts leads to a range of osteolytic bone diseases including osteoporosis, aseptic prosthesis loosening, rheumatoid arthritis, and osteoarthritis. Receptor activator of nuclear factor kappa-B ligand (RANKL) and its downstream signaling pathways are recognized as key mediators that drive the formation and activation of osteoclastic function. Hence, osteoclast formation and/or its function remain as dominant targets for research and development of agents reaching the treatment towards osteolytic diseases. Chrysin (CHR) is a flavonoid with a wide range of anti-inflammatory and anti-tumor effects. However, its effect on osteoclasts remains unknown. In this study, we found the effects of CHR on inhibiting osteoclast differentiation which were assessed in terms of the number and size of TRAcP positive multinucleated osteoclasts (OCs). Further, the inhibitory effects of CHR on bone resorption and osteoclast fusion of pre-OC were assessed by hydroxyapatite resorption pit assay and F-actin belts staining; respectively. Western blotting analysis of RANKL-induced signaling pathways and immunofluorescence analysis for p65 nuclear translocation in response to RANKL-induced osteoclasts were used to analyze the mechanism of action of CHR affecting osteoclasts. Lastly, the murine calvarial osteolysis model revealed that CHR could protect against particle-induced bone destruction in vivo. Collectively, our data strongly suggested that CHR with its promising anti-tumor effects would also be a potential therapeutic agent for osteolytic diseases.

Sandblasted/Acid-Etched Titanium Surface Modified with Calcium Phytate Enhances Bone Regeneration in a High-Glucose Microenvironment by Regulating Reactive Oxygen Species and Cell Senescence

“…Exposure of macrophages to titanium particles released into the surrounding tissue after implant placement − can significantly increase ROS production, inducing NF-κB activation and local inflammation, leading to decreased osteoblast function and increased osteoclast activity. The inflammatory process is closely linked to oxidative stress, which is caused by an imbalance of oxidant formation and degradation.…”

The Dopamine D1 Receptor Attenuates Titanium Particle-Induced Inhibition of Osteogenesis by Activating the Wnt Signaling Pathway

“…Osteoclast activation and local inflammatory response play a nonnegligible role in titanium particle-induced osteolysis. Titanium particles can cause monocytes/macrophages to trigger the release of proinflammatory factors, initiate an inflammatory cascade response, release osteoclasts, promote osteoclast recruitment, migration, and differentiation, and ultimately activate bone resorption, leading to osteolysis [ 38 ]. Panicker et al [ 39 ] reported that DA inhibited NLRP3 inflammasome activation via D1R, thereby regulating inflammation.…”

Graphene Oxide-Modified Concentric Microgrooved Titanium Surfaces for the Dual Effects of Osteogenesis and Antiosteoclastogenesis

“…The process of bone remodeling on titanium implant surfaces involves interactions among osteoclast precursor cells, osteoclasts, mesenchymal stem cells, and osteoblasts. Only by maintaining the balance of bone resorption and bone formation can the stability of bone tissue be maintained . Therefore, the effect of the implant surface on osteogenesis, its regulation of osteoclastogenic differentiation, and the interaction between them needs to be further explored.…”

“…Only by maintaining the balance of bone resorption and bone formation can the stability of bone tissue be maintained. 27 Therefore, the effect of the implant surface on osteogenesis, its regulation of osteoclastogenic differentiation, and the interaction between them needs to be further explored. In this study, we simulated the morphology of the osteon and applied a GO coating to the substrate and then verified the regulation of osteogenic and osteoclastogenic differentiation by the composite modified material in single and indirect cocultures.…”