Thiostrepton and miR-216b synergistically promote osteosarcoma cell cytotoxicity and apoptosis by targeting FoxM1.

Osteosarcoma is a common primary bone cancer that there are currently no effective treatment strategies for. Forkhead box M1 (FoxM1) is key in the development of osteosarcoma, and microRNA (miR)-216b serves an antitumor role by targeting FoxM1. Moreover, thiostrepton (TST), a natural thiazole antibiotic, induces antitumor effects and specifically targets FoxM1. Therefore, the present study investigated whether thiostrepton and miR-216b synergistically inhibited osteosarcoma cells by targeting FoxM1. The MTT assay, reverse transcription-quantitative PCR, a dual-luciferase reporter assay and flow cytometry were performed. Compared with the human osteoblast cell line hFOB1.19, miR-216b expression was significantly downregulated in the osteosarcoma cell lines U2OS, MG63 and Saos-2. By contrast, FoxM1 expression was significantly upregulated in osteosarcoma cell lines compared with the hFOB1.19 cell line. The results indicated that miR-216b targeted the 3'-untranslated region of FoxM1. Moreover, the results suggested that miR-216b cooperated with TST to decrease cell cytotoxicity and increase cell apoptosis. In addition, miR-216b cooperated with TST to increase Bax expression and decrease Bcl-2 expression. In conclusion, the combination of TST and miR-216b synergistically promoted osteosarcoma cell cytotoxicity and apoptosis by targeting FoxM1. Therefore, the present study suggested that the combination of TST and miR-216b may serve as a promising therapeutic strategy for osteosarcoma.

[Effect of percutaneous kyphoplasty on lumbar-pelvic correlation in osteoporotic vertebral compressive fractures].

OBJECTIVE: To explore the effect of percutaneous kyphoplasty (PKP) on lumbar-pelvic correlation in osteoporotic vertebral compressive fracture (OVCF). METHODS: According to the inclusion criteria, 63 patients with primary osteoporosis between January 2012 and June 2017 were selected as the control group and 67 patients with single-segment lumbar OVCF receiving PKP and complete clinical data were included as the observation group. There was no significant difference in gender, age, and lumbar spine bone density between the two groups ( P>0.05). The visual analogue scale (VAS) score and Oswestry Disability Index (ODI) score were used to assess lumbar pain and function before operation and at 3 days after operation in the observation group; lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were measured in lumbar lateral X-ray films which were taken before PKP and at 1 month after PKP. The same parameters were measured in the lumbar lateral X-ray films which were taken at the time of initial diagnosis in the control group. RESULTS: All patients were followed up 3-24 months with an average of 5.8 months in the observation group. The VAS score decreased from 5.6±1.8 before PKP to 2.8±1.3 at 3 days after PKP ( t=14.082, P=0.000); ODI decreased from 50.1%±5.0% before PKP to 18.2%±1.8% ( t=47.011, P=0.000). Compared with the control group, the LL, PI, and SS decreased and the PT increased in the observation group, and only the difference in LL between the two groups was significant ( P<0.05). In the observation group, the LL and SS significantly increased ( P<0.05) and PT significantly decreased ( P<0.05) at 1 month after operation when compared with preoperative ones, and PI decreased, but the difference was not significant ( P>0.05). In the control group, LL was positively correlated with PI and SS ( P<0.05); PI was positively correlated with PT and SS ( P<0.05). In the observation group, PI was positively correlated with SS ( P<0.05) before and after PKP. CONCLUSION: OVCF patients lost the specific lumbar-pelvic correlation. PKP can restore lumbar lordosis, but it still can not restore the normal physiological fitting.

[Effect of anterior cervical discectomy and decompression with different fusion segments on sagittal spine-pelvis balance].

Objective: To explore the effect on sagittal spine-pelvis balance of different fusion segments in anterior cervical discectomy and fusion (ACDF). Methods: The clinical data of 326 patients with cervical spondylotic myelopathy, treated by ACDF between January 2010 and December 2016, was retrospectively analysed. There were 175 males and 151 females with an average age of 56 years (range, 34-81 years). Fusion segments included single segment in 69 cases, double segments in 85 cases, three segments in 90 cases, and four segments in 82 cases. Full spine anterolateral X-ray films were performed before operationand at 12 months after operation. The spine-pelvis parameters of fusion segments were measured and compared. The parameters included C 0-2 Cobb angle, C 2-7 Cobb angle, C 2-7 sagittal vertical axis (C 2-7 SVA), T 1 slope (T 1S), thoracic inlet angle (TIA), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), C 7 sagittal vertical axis (C 7 SVA), T 1 pelvic angle (TPA). The Japanese Orthopaedic Association (JOA) score of cervical spine and visual analogue scale (VAS) scores of pain of cervical spine and upper extremity were compared before operation and at 12 months after operation. Pearson correlation analysis was performed on LL, PI, SS, C 7 SVA, and TPA before and after operation to evaluate the changes of spine-pelvis fitting relationship after ACDF. Results: All 326 patients were followed up 12-32 months (mean, 18.5 months). During the follow-up period, internal fixator was in place, and no spinal cord nerve or peripheral soft tissue injury was found. JOA scores and cervical VAS scores improved significantly at 12 months after operation ( P<0.05), no significant difference was found in VAS scores of upper extremity when compared with preoperative scores ( P>0.05). The preoperative cervical VAS scores and the postoperative JOA scores at 12 months had significant differences between groups ( P<0.05). At 12 months after operation, there was no significant difference in sagittal spine-pelvis parameters in the single segment group compared with preoperative ones ( P>0.05); but the C 0-2 Cobb angle, C 2-7 Cobb angle, C 2-7 SVA, T 1S, TIA, C 7 SVA, and TPA in the double segments, three segments, and four segments groups were significant larger than preoperative ones ( P<0.05). The C 0-2 Cobb angle, C 2-7 Cobb angle, T 1S, C 7 SVA, and TPA among 4 groups had significant differences before operation and at 12 months after operation ( P<0.05). At 12 months after operation, the changes of C 7 SVA and TPA in the double segments, three segments, and four segments groups were significantly larger than those in the single segment group ( P<0.05). PI had positive correlations with LL and SS before and after operation in 4 groups ( P<0.05). Conclusion: Normal fitting relationship between lumbar spine and pelvis in physiological state also exists in patients with cervical spondylotic myelopathy, and ACDF can not change this specific relationship. In patients with cervical spondylotic myelopathy, the sagittal spine-pelvis sequence do not change after ACDF single-level fusion, while the sagittal spine-pelvis balance change after double-level and multi-level fusion.

Biocompatibility of artificial bone based on vancomycin loaded mesoporous silica nanoparticles and calcium sulfate composites.

The aim of this study was to evaluate the in vitro and in vivo biocompatibility of artificial bone based on vancomycin loaded mesoporous silica nanoparticles and calcium sulfate composites. In vitro cytotoxicity tests by cholecystokinin octapeptide (CCK-8) assay showed that the 5%Van-MSN-CaSO4 and Van-CaSO4 bone cements were cytocompatible for mouse osteoblastic cell line MC3T3-E1. The microscopic observation confirmed that MC3T3-E1cells incubated with Van-CaSO4 group and 5%Van-MSN-CaSO4 group exhibited clear spindle-shaped changes, volume increase and maturation, showing that these cements supported adhesion of osteoblastic cells on their surfaces. In addition, the measurement of alkaline phosphatase activity revealed the osteoconductive property of these biomaterials. In order to assess in vivo biocompatibility, synthesized cements were implanted into the distal femur of twelve adult male and female New Zealand rabbits. After implantation in artificial defects of the distal femur, 5%Van-MSN-CaSO4 and Van-CaSO4 bone cements did not damage the function of main organs of rabbits. In addition, the Van-MSN-CaSO4 composite allowed complete repair of bone defects with new bone formation 3 months after implantation. These results show potential application of Van-MSN-CaSO4 composites as bone graft materials for the treatment of open fracture in human due to its mechanical, osteoconductive and potential sustained drug release characteristics and the absence of adverse effects on the body.

Bone cement based on vancomycin loaded mesoporous silica nanoparticle and calcium sulfate composites.

A novel bone cement pellet, with sustained release of vancomycin (VAN), was prepared by mixing VAN loaded mesoporous silica nanoparticle (MSN) and calcium sulfate α-hemihydrate (CS) together. To improve the VAN loading ability, MSN was functionalized with aminopropyltriethoxysilane (APS) to give APS-MSN. The VAN loading content and entrapment efficiency of APS-MSN could reach up to 45.91±0.81% and 84.88±1.52%, respectively, much higher than those of MSN, which were only 3.91% and 4.07%, respectively. The nitrogen adsorption-desorption measurement results demonstrated that most of the VAN were in the pores of APS-MSN. The CS/VAN@APS-MSN composite pellet showed a strongly drug sustained release effect in comparison with CS control pellet. The in vitro cell assays demonstrated that CS/APS-MSN composite was highly biocompatible and suitable to use as bone cement. Furthermore, CS/VAN@APS-MSN pellet showed no pyrogenic effect and meet the clinical requirements on hemolytic reaction. These results imply that CS/VAN@APS-MSN was an ideal candidate to replace CS bone cement in the treatment of open fractures.