BACKGROUND:Bovine bone matrix is a natural material that has been used in the treatment of bone lesions. In this study, bovine bone matrix Nukbone® (NKB) was investigated due its osteoconductive and osteoinductive properties. This biomaterial induces CBFA-1 activation and osteogenic differentiation, although the cytokines involved in these processes is still unknown. OBJECTIVE:The aim of this work was to determine the influence of NKB on the pro-osteoblastic and anti-osteoblastic cytokines secretion from human mesenchymal stem cells (hMSCs). METHODS:The hMSCs were cultured onto NKB and cytokines IL-2, IL-4, IL-6, IL-10, IL-12, IFN-γ and TNF-α were analized at 0-14 days by immunoassay. In addition, hemocompatibility of NKB and characterization of hMSCs were evaluated. RESULTS:NKB induces an increase on pro-osteoblastic cytokine secretion IL-4 and a decrease on anti-osteoblastic cytokine IL-6 secretion, at days 7 and 14 of cell culture. Interestingly, there was no statistical difference between secretion profiles of others cytokines analized. CONCLUSIONS:The up-regulation of IL-4 and down-regulation of IL-6, and the secretion profiles of other cytokines examined in this work, are findings that will contribute to the understanding of the role of NKB, and similar biomaterials, in bone homeostasis and in the osteoblastic differentiation of hMSCs.

中文翻译：

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牛骨基质诱导人间充质干细胞分泌细胞因子

背景：牛骨基质是一种天然材料，已被用于治疗骨病变。在这项研究中，牛骨基质 Nukbone® (NKB) 由于其骨传导和骨诱导特性而被研究。这种生物材料诱导 CBFA-1 活化和成骨分化，尽管这些过程中涉及的细胞因子仍然未知。目的：本工作的目的是确定NKB对人间充质干细胞（hMSCs）分泌前成骨细胞和抗成骨细胞细胞因子的影响。方法：将hMSCs培养在NKB上，0-14天免疫分析检测细胞因子IL-2、IL-4、IL-6、IL-10、IL-12、IFN-γ和TNF-α。此外，还评估了 NKB 的血液相容性和 hMSC 的特征。结果：在细胞培养的第 7 天和第 14 天，NKB 诱导前成骨细胞细胞因子分泌 IL-4 增加和抗成骨细胞细胞因子 IL-6 分泌减少。有趣的是，分析的其他细胞因子的分泌谱之间没有统计学差异。结论：IL-4 的上调和 IL-6 的下调，以及本工作中检查的其他细胞因子的分泌谱，这些发现将有助于理解 NKB 和类似生物材料在骨稳态和 hMSC 的成骨细胞分化。