Vaccarin prevents titanium particle-induced osteolysis and inhibits RANKL-induced osteoclastogenesis by blocking NF-κB and MAPK signaling pathways.

Wearing titanium particle-induced osteoclastogenesis, accompanied by peri-implant osteolysis, is the main cause of long-term failure of hip prosthesis. Currently, medications used for the prevention and treatment of peri-implant osteolysis show serious side effects. Therefore, development for more effective new drugs with less side effects is extremely urgent. Vaccarin is a natural flavonoid extracted from Vaccaria segetalis, with various biological functions, including antioxidantory, anti-inflammatory, and promotion of angiogenesis. However, the putative role of vaccarin in the inhibition of titanium particle-induced osteolysis has not been reported. In this study, it was indicated that vaccarin could effectively inhibit RANKL-induced osteoclastogenesis, fusion of F-actin rings, bone resorption, and expression of osteoclast marker genes in a dose-dependent manner in vitro. Moreover, vaccarin could also inhibit RANKL-induced osteoclastogenesis via the inhibition of NF-κB and MAPK (p38, ERK, and JNK) signaling pathways, and inhibit the transcription of downstream transcription factors, such as c-Fos and NFATc1. Consistent with in vitro results, this in vivo study showed that vaccarin exhibited an inhibitory effect on titanium particle-induced osteolysis by antiosteoclastogenesis. In conclusion, vaccarin could be a promising agent for preventing and treating peri-implant osteolysis.

A study on the prevention and treatment of murine calvarial inflammatory osteolysis induced by ultra-high-molecular-weight polyethylene particles with neomangiferin.

The present study aimed to examine the influence of neomangiferin on murine calvarial inflammatory osteolysis induced by ultra-high-molecular-weight polyethylene (UHMWPE) particles. Eight-week-old male C57BL/J6 mice served as an inflammatory osteolysis model, in which UHMWPE particles were implanted into the calvarial subperiosteal space. The mice were randomly distributed into four groups and treated with different interventions; namely, a sham group [phosphate-buffered saline (PBS) injection and no UHMWPE particles], model group (PBS injection and implantation of UHMWPE particles), low-dose neomangiferin group (UHMWPE particles +2.5 mg/kg neomangiferin), and high-dose neomangiferin group (UHMWPE particles +5 mg/kg neomangiferin). Following 3 weeks of feeding according to the above regimens, celiac artery blood samples were collected for an enzyme-linked immunosorbent assay (ELISA) to determine the expression of receptor activator of nuclear factor-κB ligand (RANKL), osteoclast-related receptor (OSCAR), cross-linked C-telopeptide of type I collagen (CTX-1); osteoprotegerin (OPG), tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß. Subsequently, the mice were sacrificed by cervical dislocation following ether-inhalation anesthesia, and the skull was separated for osteolysis analysis by micro-computed tomography (micro-CT). Following hematoxylin and eosin staining, tartrate-resistant acid phosphatase (TRAP) staining was performed to observe the dissolution and destruction of the skull. The micro-CT results suggested that neomangiferin significantly inhibited the murine calvarial osteolysis and bone resorption induced by UHMWPE particles. In addition, the ELISA results showed that neomangiferin decreased the expression levels of osteoclast markers RANKL, OSCAR, CTX-1, TNF-α and IL-1ß. By contrast, the levels of OPG increased with the neomangiferin dose. Histopathological examination revealed that the TRAP-positive cell count was significantly reduced in the neomangiferin-treated animals compared with that in the positive control group, and the degree of bone resorption was also markedly reduced. Neomangiferin was found to have significant anti-inflammatory effects and to inhibit osteoclastogenesis. Therefore, it has the potential to prevent the aseptic loosening of a prosthesis following artificial joint replacement.