Wang Hong-Tao, Li Jia, Ma Shi-Ting, Feng Wen-Yu, Wang Qi, Zhou Hong-Yan, Zhao Jin-Min, Yao Jun
Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Orthopedic Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Exp Ther Med. 2018 Nov;16(5):3889-3896. doi: 10.3892/etm.2018.6725. Epub 2018 Sep 11.
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.
本研究旨在探讨新芒果苷对超高分子量聚乙烯（UHMWPE）颗粒诱导的小鼠颅骨炎性骨溶解的影响。8周龄雄性C57BL/J6小鼠作为炎性骨溶解模型，将UHMWPE颗粒植入颅骨骨膜下间隙。小鼠被随机分为四组并接受不同干预；即假手术组（注射磷酸盐缓冲盐水（PBS）且不植入UHMWPE颗粒）、模型组（注射PBS并植入UHMWPE颗粒）、低剂量新芒果苷组（UHMWPE颗粒+2.5mg/kg新芒果苷）和高剂量新芒果苷组（UHMWPE颗粒+5mg/kg新芒果苷）。按照上述方案喂养3周后，采集腹腔动脉血样本进行酶联免疫吸附测定（ELISA），以测定核因子κB配体受体激活剂（RANKL）、破骨细胞相关受体（OSCAR）、I型胶原交联C末端肽（CTX-1）、骨保护素（OPG）、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β的表达。随后，在乙醚吸入麻醉后通过颈椎脱臼处死小鼠，并分离颅骨进行显微计算机断层扫描（micro-CT）分析骨溶解情况。苏木精-伊红染色后，进行抗酒石酸酸性磷酸酶（TRAP）染色以观察颅骨的溶解和破坏情况。micro-CT结果表明，新芒果苷显著抑制了UHMWPE颗粒诱导的小鼠颅骨骨溶解和骨吸收。此外，ELISA结果显示，新芒果苷降低了破骨细胞标志物RANKL、OSCAR、CTX-1、TNF-α和IL-1β的表达水平。相比之下，OPG水平随新芒果苷剂量增加而升高。组织病理学检查显示，与阳性对照组相比，新芒果苷处理的动物中TRAP阳性细胞计数显著减少，骨吸收程度也明显降低。发现新芒果苷具有显著的抗炎作用并抑制破骨细胞生成。因此，它有可能预防人工关节置换后假体的无菌性松动。
