Delayed Expression of Circulating TGF-β1 and BMP-2 Levels in Human Nonunion Long Bone Fracture Healing

J Nippon Med Sch. 2017;84(1):12-18. doi: 10.1272/jnms.84.12.


Background: The healing process of bone fracture requires a well-controlled multistage and sequential order beginning immediately after the injury. However, complications leading to nonunion exist, creating serious problems and costs for patients. Transforming growth factor-beta 1 (TGF-β1) and bone morphogenic protein 2 (BMP-2) are two major growth factors involved in human bone fracture healing by promoting various stages of bone ossification. In this study, we aimed to determine the role of these factors during the fracture healing of human long bones and assess their impacts on nonunion condition.

Materials and methods: We performed a comprehensive analysis of plasma TGF-β1 and BMP-2 levels in blood samples from 10 patients with proved nonunion and 10 matched patients with normal union following a predetermined time schedule. The concentrations of TGF-β1 and BMP-2 were measured at each time point using a solid-phase ELISA.

Results: TGF-β1 and BMP-2 levels were detectable in all patients. For all patients, a maximal peak for TGF-β1 was found at 3-week. In normal union group, TGF-β1 showed a maximal peak at 2-week while nonunion group had a delayed maximal peak at 3-week. Plasma levels of BMP-2 for all patients and for normal union group reached a maximal peak at 1-week, but nonunion group showed a delayed maximal peak at 2-week. In general, plasma TGF-β1 or BMP-2 level was not significantly different between normal union and nonunion groups.

Conclusion: The expression levels of TGF-β1 and BMP-2 appeared to be delayed in nonunion patients which could play an important role in developing an early marker of fracture union condition and facilitate improved patient's management.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Bone Morphogenetic Protein 2 / blood*
  • Bone Morphogenetic Protein 2 / physiology
  • Female
  • Fracture Healing / genetics*
  • Fracture Healing / physiology*
  • Fractures, Bone / genetics*
  • Fractures, Bone / physiopathology*
  • Fractures, Malunited / diagnosis*
  • Fractures, Malunited / genetics*
  • Gene Expression*
  • Humans
  • Male
  • Middle Aged
  • Time Factors
  • Transforming Growth Factor beta1 / blood*
  • Transforming Growth Factor beta1 / physiology
  • Young Adult


  • BMP2 protein, human
  • Biomarkers
  • Bone Morphogenetic Protein 2
  • Transforming Growth Factor beta1