Molecular pathogenesis of fracture nonunion

Abstract

Fracture nonunion, a serious bone fracture complication, remains a challenge in clinical practice. Although the molecular pathogenesis of nonunion remains unclear, a better understanding may provide better approaches for its prevention, diagnosis and treatment at the molecular level. This review tries to summarise the progress made in studies of the pathogenesis of fracture nonunion. We discuss the evidence supporting the concept that the development of nonunion is related to genetic factors. The importance of several cytokines that regulate fracture healing in the pathogenesis of nonunion, such as tumour necrosis factor-α, interleukin-6, bone morphogenetic proteins, insulin-like growth factors, matrix metalloproteinases and vascular endothelial growth factor, has been proven in vitro, in animals and in humans. Nitric oxide and the Wnt signalling pathway also play important roles in the development of nonunion. We present potential strategies for the prevention, diagnosis and treatment of nonunion, and the interaction between genetic alteration and abnormal cytokine expression warrants further investigation.

The translational potential of this article: A better understanding of nonunion molecular pathogenesis may provide better approaches for its prevention, diagnosis and treatment in clinical practice.

Keywords: Cytokine; Gene; Molecular pathogenesis; Nonunion.

Figure 1

The pathogenesis of nonunion at molecular level. Both environmental risk factors and genetic factors lead to the abnormal expression of cytokines, which is the key point for nonunion development. Genetic factors and abnormal cytokine expression, at the molecular level, are discussed in this review. BMP = bone morphogenetic protein; IGF = insulin-like growth factor; IL = interleukin; MMP = matrix metalloproteinase; SNP = single nucleotide polymorphism; TNF-α = tumour necrosis factor-α; VEGF = vascular endothelial growth factor.