RESUMO
Periprosthetic osteolysis is one of the major long-term complications following total joint replacement. Its cause is widely accepted to be wear particle-induced activation of inflammatory macrophages. No effective strategy for the prevention and treatment of periprosthetic osteolysis is yet available. Recently, considerable evidence has shown that icariin effectively protects against estrogen deficiency-related bone loss and bone deterioration. However, the molecular mechanism underlying the inhibitory effect of icariin on wear particle-induced periprosthetic osteolysis is not yet clear. In this study, nanoscale CoCrMo wear particles were obtained by high-vacuum three-electrode direct current from the femoral head implant of a patient diagnosed with aseptic loosening. The effects of icariin on wear particle-induced expression of proinflammatory factors, NF-κB signaling modulation, osteolysis, and estrogen receptor α (ERα) activation were evaluated in vitro and in vivo using bone marrow-derived macrophages and C57/BL6J mice, respectively. A possible link between ERα and the protective effect of icariin was further studied using an ERα antagonist and the ERα-siRNA interference. Chemical composition analysis showed that Cr and Co were the major metallic elements of the nanoscale particles, with a mean size of 150.2 ± 37.4 nm for the CoCrMo particles. Following icariin treatment, significant decreases were observed in CoCrMo wear particle-induced TNF-α and IL-6 mRNA expression in BMDMs, and osteolysis in mice calvaria. Marked decreases in the protein expression level of p-IKKß, p-p65 and p-IκBα were also observed, together with significant decreases in the nuclear import of P65 and macrophage M1 polarization. RNA sequencing revealed that ERα was closely associated with TNF-α and IL-6 in wear particle-stimulated macrophages. Furthermore, marked increases in phospho-ERα Ser118 and phospho-ERα Ser167 protein expression and the nuclear import of ERα were also found in the icariin group. The protective effects of icariin on CoCrMo particle-induced mouse calvarial osteolysis and on the inflammation response in BMDMs were reversed by ERα antagonist and by ERα-siRNA interference. In conclusion, icariin attenuates wear particle-induced inflammation and osteolysis via down-regulation of the ERα-mediated NF-κB signaling pathway in macrophages. The potential application of icariin as a non-hormonal therapy for wear particle-induced periprosthetic osteolysis is worthy of further investigation.
RESUMO
Objective:To evaluate the safety and efficacy of the treatment for oppressive spinal by microwave ablation combined with percutaneous fixation and open decompression.Methods:From January 2015 to September 2018, 20 patients with 26 spinal metastatic were treated with microwave ablation combined with percutaneous fixation and open decompression, including 13 males and 7 females with an average age of 43.85±18.67 years (range, 16-79 years). The locations of the lesions included: 9 in the thoracic, 11 in the lumbar. The tumors' type: myeloma 2 cases, leukemia 1 case, liver cancer 4 cases, osteosarcoma 2 cases, lung cancer 5 cases, kidney cancer 1 case, esophagus cancer 1case, cervical cancer 1 case, intestinal cancer 1 case, prostate cancer 1 case, adenoid cystic cancer 1case. Preoperatively all the patients suffered with the local pain and the spinal cord or nerve root compression symptoms. All 20 cases were examined with CT or MRI to determine the lesions and the sizes of metastasis, as well as to evaluate the ablation zone. The entry of the pedicle screws were performed by Wiltse method through paravertebral muscles. After that the lesions were treated with partial resection for decompression of spinal cord or nerve root, and followed with microwave ablation at the metastasis site. Thermometer was used to monitor the temperature at the central and posterior edges of the vertebral body. The surrounding important tissue were cooled by ice saline. 13 patients were performed with vertebroplasty for enhancement the intensity of the vertebral body. The visual analogue scale (VAS) score was used to evaluate the effect of pain relief after surgery. The postoperative neurological function and performance status were evaluated using Frankel grading and Eastern Cooperative Oncology Group (ECOG).Results:Each lesion was heated for 5.43±2.07 min (range, 3-10 min). The power of microwave ablation was 40-60 W. The mean blood loss during operation was 852.50±514.40 ml (range, 100-1 700 ml). The mean operating time was 4.11±0.99 h (range, 2.5-6.0 h). The temperature inside the lesion was 70-85 ℃. The temperature of the surrounding tissue was maintained at<43 ℃ by repeated frozen saline flush. All cases were followed up for 8.45±2.01 months (range, 6-14 months) without any recurrence. The VAS score of the 20 patients at 48 h, 1 month, 3 months and 6 months after operation were 1.55±1.23, 2.70±0.87, 2.40±1.14 and 3.05±1.00 points, which were all statistically lowerthan the preoperative score 5.95±1.18 ( P<0.05). The Frankel grading of 14 patients had at least one grade improvement 6 months after operation. There were 8 patients shown markedly improved ECOG score 6 months after surgery. Only one case suffered from reduced myodynamiaof lower limb and covered in one month after system treatment. Conclusion:The microwave ablation combined with percutaneous fixation and open decompression could resolve the spinal and nerve compression, relieve the pain in metastatic spinal oppression, reconstruct the stability, and improve the quality of lives, which is a safe and effective palliative surgical method.
