Laboratory for Orthopedic Pathophysiology and Regenerative Medicine, Rizzoli Orthopedic Institute, Bologna 1/10, Bologna 40136, Italy.
J Orthop Res. 2013 Feb;31(2):249-56. doi: 10.1002/jor.22219. Epub 2012 Sep 14.
Fibroblast growth factor 2 (FGF-2) plays an important role in the early phases of bone healing. In this study, we measured FGF-2 serum levels in 88 children undergoing surgical treatment for congenital (n = 49) or acquired (n = 39) orthopedic conditions, which were associated (n = 35) or not (n = 53) with bone lesions, to assess whether serum levels of FGF-2 varied according to the underlying disease and may predict clinical outcomes. FGF-2 serum levels were significantly lower in patients who did not heal after surgery (p = 0.008). Diagnostic accuracy was validated statistically, and the ROC curve provided a threshold value useful in discriminating good versus poor outcomes. The relationship between FGF-2 and bone healing was supported by in vitro experiments. A mineralization assay was performed on bone marrow stromal cells from three patients with congenital pseudarthrosis, who had low serum levels of FGF-2 and a poor clinical outcome after surgical treatment. Autologous serum alone was not sufficient to induce in vitro mineralization, but it did occur when cells were cultured with different sources of exogenous growth factors (GFs), including recombinant FGF-2 and homologous serum collected from children with fractures, high FGF-2 levels, and a good clinical outcome. In conclusion, our findings suggest that osteoinductive GFs are essential for bone repair, and that the amount of circulating FGF-2 may predict bone healing.
成纤维细胞生长因子 2(FGF-2)在骨愈合的早期阶段发挥着重要作用。在这项研究中,我们测量了 88 名接受先天性(n = 49)或后天性(n = 39)骨科疾病手术治疗的儿童的 FGF-2 血清水平,这些疾病与(n = 35)或不与(n = 53)骨损伤有关,以评估 FGF-2 血清水平是否根据潜在疾病而有所不同,并且可能预测临床结果。手术后未愈合的患者(p = 0.008)的 FGF-2 血清水平明显降低。通过统计验证了诊断准确性,ROC 曲线提供了用于区分良好和不良结局的有用阈值。体外实验支持 FGF-2 与骨愈合之间的关系。对三名先天性假关节患者的骨髓基质细胞进行矿化试验,这些患者的 FGF-2 血清水平较低,手术后临床结果不佳。单独使用自体血清不足以诱导体外矿化,但当细胞在培养时,使用不同来源的外源性生长因子(GFs),包括重组 FGF-2 和来自骨折、高 FGF-2 水平和良好临床结果的儿童的同源血清,矿化就会发生。总之,我们的研究结果表明,成骨诱导性 GFs 对于骨修复至关重要,并且循环 FGF-2 的量可能预测骨愈合。