RESUMEN
Bone regeneration and mineralization can be achieved by means of distraction osteogenesis (DO). In the present study, we investigated the effect of stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) on the new bone formation during DO in rats. Forty-eight Sprague-Dawley rats were randomized into four groups of 12 rats each. We established the left femoral DO model in rats and performed a mid-femoral osteotomy, which was fixed with an external fixator. DO was performed at 0.25 mm/12 h after an incubation period of 5 days. Distraction was continued for 10 days, resulting in a total of 5 mm of lengthening. After distraction, the solution was locally injected into the osteotomy site, once a day 1 ml for 1 week. One group received the solvent alone and served as the control, and the other three groups were treated with SDF-1, VEGF, and SDF-1with VEGF in an aqueous. Sequential X-ray radiographs were taken two weekly. The regeneration was monitored with the use of micro-CT analysis, mechanical testing, and histology. Radiographs showed accelerated regenerate ossification in the SDF-1, VEGF, and SDF-1 with the VEGF group, with a larger amount of new bone compared with the control group, especially SDF-1 with the VEGF group. Micro-CT analysis and biomechanical tests showed Continuous injection of the SDF-1, VEGF, and SDF-1 with VEGF during the consolidation period significantly increased bone mineral density bone volume, mechanical maximum loading, and bone mineralization of the regenerate. Similarly, the expression of osteogenic-specific genes, as determined by real-time polymerase chain reaction , was significantly higher in SDF-1 with the VEGF group than in the other groups. Histological examination revealed more new trabeculae in the distraction gap and more mature bone tissue for the SDF-1 with the VEGF group. SDF-1 and VEGF promote bone regeneration and mineralization during DO, and there is a synergistic effect between the SDF-1 and VEGF. It is possible to provide a new and feasible method to shorten the period of treatment of DO.
RESUMEN
AIMS: Sulforaphene (SFE), a naturally occurring isothiocyanate found in cruciferous vegetables, has attracted increasing attention for its anti-cancer effect in many cancers. MAIN METHODS: We explored the therapeutic effects of SFE in modulating the progression of osteosarcoma. CCK8 assay, colony formation assay, western blot, wounding healing assay and transwell assay were conducted to detect the proliferation, apoptosis, migration and invasion of osteosarcoma cells (U2OS and Saos2) treated with different concentrations of SFE. In addition, tumor xenograft in nude mice is performed to test the effects of SFE in tumorigenesis in vivo. Moreover, the levels of FSTL1 and NF-κB were determined by western blot, and loss of functions of FATL1 and NF-κB were further conducted to evaluate the underlying mechanisms of SFE on osteosarcoma development. KEY FINDINGS: The results revealed that SFE inhibited the growth while promoted apoptosis of U2OS and Saos2 cells in a dose-dependent manner. Mechanistically, SFE significantly inhibited the expression of NF-κB and FSTL1. However, the genetic intervention of FSTL1 or pharmacologically inhibiting NF-κB weakened the anti-tumor role of SFE. SIGNIFICANCE: This study suggested that SFE alleviates the progression of osteosarcoma through modulating the FSTL1/NF-κB pathway.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Proteínas Relacionadas con la Folistatina/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Isotiocianatos/farmacología , FN-kappa B/metabolismo , Osteosarcoma/tratamiento farmacológico , Animales , Apoptosis , Biomarcadores de Tumor/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Proliferación Celular , Progresión de la Enfermedad , Proteínas Relacionadas con la Folistatina/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , FN-kappa B/genética , Osteosarcoma/metabolismo , Osteosarcoma/patología , Transducción de Señal , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Objective: To review the research progress of the role of periosteum in distraction osteogenesis. Methods: The related domestic and foreign literature about the role of periosteum in distraction osteogenesis in recent years was extensively reviewed, summarized, and the mechanism and influencing factors of periosteum during traction and osteogenesis were analyzed. Results: The periosteum is rich in all kinds of cells (mesenchymal stem cells, osteoblasts, etc.), microvessel and various growth factors, which are necessary for the formation of new bone. It can promote the formation of new bone in the process of traction osteogenesis significantly. Conclusion: The periosteum plays an important role in the progress of distraction osteogenesis.