Elevated transforming growth factor-beta 1 (TGF-β1) levels in human fracture healing

Abstract

IntroductionTransforming growth factor-beta 1(TGF-β1) is a regulatory protein, involved in bone fracture healing. Circulating TGF-β1 levels have been reported to be a predictor of delayed bone healing and non-union, suggesting active relationship between tissue and circulating TGF-β1 in fracture healing. The purpose of this study was to analyse TGF-β1 local and serum concentrations in fracture healing to further contribute to the understanding of molecular regulation of fracture healing.Patients and methodsSerum samples of 113 patients with long bone fractures were collected over a period of 6 months following a standardised time schedule. TGF-β1 serum concentrations were measured using ELISA. Patients were assigned to 2 groups: Group 1 contained 103 patients with physiological healing. Group 2 contained 10 patients with impaired healing. Patients in both groups were matched. One patient of the group 2 had to be excluded because of missing match partner. In addition, fracture haematoma from 11 patients of group 1 was obtained to analyse local TGF-β1 concentrations. 33 volunteers donated serum which served as control.ResultsTGF-β1 serum concentrations increased during the early healing period and were significantly higher in patients with physiological healing compared to controls (P = 0.04). Thereafter, it decreased continuously between weeks 2 and 8 and fell again after week 8. TGF-β1 serum concentrations in patients with physiological healing were significantly higher at week 24 compared to controls (P = 0.05). In non-unions, serum concentrations differed significantly from those of controls at week 6 (P = 0.01). No significant difference in between patients with physiological and impaired fracture healing was observed. Fracture haematoma contained significantly higher TGF-β1 concentrations than peripheral serum of the patients (P = 0.017).ConclusionElevated levels of TGF-β1 in haematoma and in serum after bone fracture especially during the entire healing process indicate its importance for fracture healing.

Is the expression of Transforming Growth Factor-Beta1 after fracture of long bones solely influenced by the healing process?

“…In a recent study our group demonstrated a significant increase in the TGF-β1 concentration in fracture haematoma and in serum of patients with long bone fracture. These results indicated the importance of this cytokine for fracture healing and confirmed other clinical and experimental studies [8][9][10][11][12][13][14][15][16][17]. Circulating TGF-β1 levels were found to be a predictor of delayed bone healing and non-union [11].…”

“…Patients gave informed written consent to be enrolled in the study, and were 18-90 years old. The recruitment parameters, sample collection schedule, matching process, patient demographics and exclusion criteria of this study have been previously published in detail [8][9][10]. In brief, between 2006 and 2008 a consecutive series of 113 patients with meta-/ diaphyseal fractures of long bone (humerus, femur, lower leg and forearm) and surgical treatment were included.…”

“…Evidence exists that the local and systemic concentrations of different osteogenic growth factors are increased during fracture healing [8][9][10][11][12][13][14][15][16][17]. Among these factors TGF-β1 is known to be pivotal for the bone healing.…”

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

“…1 Plasma levels of TGF-β1 for all patients (A), and for normal union group (B) showed a maximal peak at 3-week and 2-week respectively while that for nonunion group (C) showed a delayed maximal peak at 3-week as compared to normal union group. 11 . Also, TGF-β1 levels were significantly higher in fracture hematoma as compared to peripheral serum of the patients but no significant difference was found between patients with normal healing and those with delayed fracture healing.…”

“…Nonunion was defined based on conventional definition as no bony healing obtained in 6 months after the fracture evidenced by specific radiological features showing bone ending changes 11 . During the course of the study, we experienced 10 patients with lower limb fracture who developed nonunion.…”