Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
Department of Histology and Embryology, Medical Faculty, Hacettepe University, Ankara, Turkey
Turk J Med Sci. 2020 Nov 3;50(SI-2):1707-1722. doi: 10.3906/sag-2003-127.
A fracture that does not unite in nine months is defined as nonunion. Nonunion is common in fragmented fractures and large bone defects where vascularization is impaired. The distal third of the tibia, the scaphoid bone or the talus fractures are furthermore prone to nonunion. Open fractures and spinal fusion cases also need special monitoring for healing. Bone tissue regeneration can be attained by autografts, allografts, xenografts and synthetic materials, however their limited availability and the increased surgical time as well as the donor site morbidity of autograft use, and lower probability of success, increased costs and disease transmission and immunological reaction probability of allografts oblige us to find better solutions and new grafts to overcome the cons. A proper biomaterial for regeneration should be osteoinductive, osteoconductive, biocompatible and mechanically suitable. Cytokine therapy, where growth factors are introduced either exogenously or triggered endogenously, is one of the commonly used method in bone tissue engineering. Transforming growth factor β (TGFβ) superfamily, which can be divided structurally into two groups as bone morphogenetic proteins (BMPs), growth differentiation factors (GDFs) and TGFβ, activin, Nodal branch, Mullerian hormone, are known to be produced by osteoblasts and other bone cells and present already in bone matrix abundantly, to take roles in bone homeostasis. BMP family, as the biggest subfamily of TGFβ superfamily, is also reported to be the most effective growth factors in bone and development, which makes them one of the most popular cytokines used in bone regeneration. Complications depending on the excess use of growth factors, and pleiotropic functions of BMPs are however the main reasons of why they should be approached with care. In this review, the Smad dependent signaling pathways of TGFβ and BMP families and their relations and the applications in preclinical and clinical studies will be briefly summarized.
如果骨折在 9 个月内仍未愈合，即可定义为骨不连。骨不连在粉碎性骨折和大的骨缺损中较为常见，因为这些部位的血管化受到损害。胫骨远端三分之一、舟状骨或距骨骨折也容易发生骨不连。开放性骨折和脊柱融合病例也需要特别监测愈合情况。骨组织再生可以通过自体移植物、同种异体移植物、异种移植物和合成材料来实现，但是它们的可用性有限，以及自体移植物使用增加的手术时间和供体部位发病率、同种异体移植物成功率较低、增加的成本和疾病传播以及免疫反应概率，促使我们寻找更好的解决方案和新的移植物来克服这些缺点。一种合适的再生生物材料应该具有骨诱导性、骨传导性、生物相容性和机械适应性。细胞因子治疗是一种常用的骨组织工程方法，其中生长因子要么外源性引入，要么内源性触发。转化生长因子 β（TGFβ）超家族，从结构上可分为骨形态发生蛋白（BMPs）、生长分化因子（GDFs）和 TGFβ、激活素、Nodal 分支、Müllerian 激素两组，已知由成骨细胞和其他骨细胞产生，并在骨基质中大量存在，在骨稳态中发挥作用。BMP 家族作为 TGFβ 超家族中最大的亚家族，也被报道是骨骼和发育中最有效的生长因子，这使得它们成为骨再生中最常用的细胞因子之一。然而，由于过度使用生长因子引起的并发症和 BMP 的多效性功能，是我们需要谨慎对待它们的主要原因。在这篇综述中，我们将简要总结 TGFβ和 BMP 家族的 Smad 依赖性信号通路及其相互关系以及在临床前和临床研究中的应用。
