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

Abstract

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)-1β. 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-1β. 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.