RESUMEN
Bone formation is driven by many signaling molecules including bone morphogenetic protein 9 (BMP-9) and hypoxia-inducible factor 1-alpha (HIF-1α). We demonstrated that cell therapy using mesenchymal stem cells (MSCs) overexpressing BMP-9 (MSCs+BMP-9) enhances bone formation in calvarial defects. Here, the effect of hypoxia on BMP components and targets of MSCs+BMP-9 and of these hypoxia-primed cells on osteoblast differentiation and bone repair was evaluated. Hypoxia was induced with cobalt chloride (CoCl2) in MSCs+BMP-9, and the expression of BMP components and targets was evaluated. The paracrine effects of hypoxia-primed MSCs+BMP-9 on cell viability and migration and osteoblast differentiation were evaluated using conditioned medium. The bone formation induced by hypoxia-primed MSCs+BMP-9 directly injected into rat calvarial defects was also evaluated. The results demonstrated that hypoxia regulated BMP components and targets without affecting BMP-9 amount and that the conditioned medium generated under hypoxia favored cell migration and osteoblast differentiation. Hypoxia-primed MSCs+BMP-9 did not increase bone repair compared with control MSCs+BMP-9. Thus, despite the lack of effect of hypoxia on bone formation, the enhancement of cell migration and osteoblast differentiation opens windows for further investigations on approaches to modulate the BMP-9-HIF-1α circuit in the context of cell-based therapies to induce bone regeneration.
RESUMEN
OBJECTIVES: This study aimed to evaluate the effects on bone repair of different concentrations of mineral trioxide aggregate (MTA) added to AH Plus. MATERIALS AND METHODS: Bone tissue reactions were evaluated in 30 rats (Rattus norvegicus) after 7 and 30 days. In the AH + MTA10, AH + MTA20, and AH + MTA30 groups, defects in the tibiae were filled with AH Plus with MTA in proportions of 10%, 20% and 30%, respectively; in the MTA-FILL group, MTA Fillapex was used; and in the control group, no sealer was used. The samples were histologically analyzed to assess bone union and maturation. The Kruskal-Wallis and Mann-Whitney tests were performed for multiple pairwise comparisons (p ≤ 0.05). RESULTS: At the 7-day time point, AH + MTA10 was superior to MTA-FILL with respect to bone union, and AH + MTA20 was superior to MTA-FILL with respect to bone maturity (p < 0.05). At the 30-day time point, both the AH + MTA10 and AH + MTA20 experimental sealers were superior not only to MTA-FILL, but also to AH + MTA30 with respect to both parameters (p < 0.05). The results of the AH + MTA10 and AH + MTA20 groups were superior to those of the control group for both parameters and experimental time points (p < 0.05). CONCLUSIONS: The results suggest the potential benefit of using a combination of these materials in situations requiring bone repair.
