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The treatment of nonunions with application of BMP-7 increases the expression pattern for angiogenic and inflammable cytokines: a matched pair analysis

View Article: PubMed Central - PubMed

ABSTRACT

The local application of bone morphogenetic protein-7 (BMP-7) in combination with the transplantation of autologous bone graft improves the outcome in nonunion treatment; however, the specific reasons remain unclear. In this study, we sought to determine if the local application of BMP-7 contributes to improved bone regeneration in nonunion therapy by modulation of the angiogenic and inflammable cytokine expression patterns of the early inflammation response. Therefore, we utilized the analysis of serological cytokine expression patterns. As a matched pair analysis, best-fitting patients who were treated with transplantation of autologous bone graft (G1, n=10) were compared with patients who were treated with additional application of BMP-7 (G2, n=10). The changes in the cytokine expression patterns were monitored and correlated to clinical data of bone healing. Significant differences in angiogenesis potential (vascular endothelial growth factor [VEGF] serum levels) could be found in the first days after surgery (P<0.05). Furthermore, the increase and absolute amount of VEGF levels in the BMP-7 group were considerably higher than in the control group during the first 2 weeks after surgery. The expression pattern of inflammable cytokines showed noticeable differences in the time point of significant elevated levels, in particular, inflammable cytokines showed an earlier peak in G2. Furthermore, interleukin-6 was significantly elevated within the first week only, comparing G2 to G1 (P<0.05). Our findings indicate that BMP-7 induces an early and more intense expression of VEGF via a direct and postulated indirect pathway, thereby providing a favorable environment for bone healing. Moreover, application of BMP-7 leads to an earlier expression of known proinflammatory cytokines. The results of this study show that application of BMP-7 leads to costimulatory effect on both angiogenic and inflammable cytokine expression patterns that may serve as a possible stimulus for bone regeneration.

No MeSH data available.


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Evaluation of the expression pattern of VEGF after nonunion treatment.Notes: (A) Serum concentrations of VEGF in pg/mL 1d before and 2d, 1w, 2w, 4w, 6w, and 12w after surgery. Significant differences are indicated by a star (P<0.05, whiskers are SD). (B) Box plot after 2d to 2w of surgery. Whiskers demonstrate one-quarter of the sample. Stars indicate significant differences comparing the study and control groups at the time point (P<0.05).Abbreviations: VEGF, vascular endothelial growth factor; p, preoperative; d, day(s); w, week(s); SD, standard deviation; BMP-7, bone morphogenetic protein-7; G1, patients who were treated with transplantation of autologous bone graft; G2, patients who were treated with additional application of BMP-7.
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f2-jir-9-155: Evaluation of the expression pattern of VEGF after nonunion treatment.Notes: (A) Serum concentrations of VEGF in pg/mL 1d before and 2d, 1w, 2w, 4w, 6w, and 12w after surgery. Significant differences are indicated by a star (P<0.05, whiskers are SD). (B) Box plot after 2d to 2w of surgery. Whiskers demonstrate one-quarter of the sample. Stars indicate significant differences comparing the study and control groups at the time point (P<0.05).Abbreviations: VEGF, vascular endothelial growth factor; p, preoperative; d, day(s); w, week(s); SD, standard deviation; BMP-7, bone morphogenetic protein-7; G1, patients who were treated with transplantation of autologous bone graft; G2, patients who were treated with additional application of BMP-7.

Mentions: Significant differences in angiogenesis potential (VEGF serum levels) could be found in the first days after surgery comparing G2 and the control groups. In detail, the VEGF serum levels in the BMP-7 group rose from day 2 after surgery to a peak on day 14 and were finally comparable to those at admission 4 weeks after surgery (Figure 2A). In contrast, the VEGF serum levels in our control group decreased after surgery on day 2 after surgery and afterward showed a VEGF time course that was comparable to the G2 group, but in contrast to this, the absolute serum levels of VEGF showed significant differences before surgical treatment (P=0.035) and on day 2 after surgery (P=0.009) comparing the study group and control group. Furthermore, the absolute increase in the VEGF serum levels between preoperative values and values at week 2 was considerably higher in the G2 group compared to the control group (absolute increase 2 weeks vs preoperative: G2, 186.60 pg/mL and G1, 100.53 pg/mL). In summary, the increase (Figure 2B) and absolute amount of VEGF levels in the BMP-7 group were considerably higher than in the control group during the first 2 weeks after surgery (G2 after 2 weeks: 351.95 pg/mL; G1 after 2 weeks: 191.57 pg/mL) as shown in Figure 2.


The treatment of nonunions with application of BMP-7 increases the expression pattern for angiogenic and inflammable cytokines: a matched pair analysis
Evaluation of the expression pattern of VEGF after nonunion treatment.Notes: (A) Serum concentrations of VEGF in pg/mL 1d before and 2d, 1w, 2w, 4w, 6w, and 12w after surgery. Significant differences are indicated by a star (P<0.05, whiskers are SD). (B) Box plot after 2d to 2w of surgery. Whiskers demonstrate one-quarter of the sample. Stars indicate significant differences comparing the study and control groups at the time point (P<0.05).Abbreviations: VEGF, vascular endothelial growth factor; p, preoperative; d, day(s); w, week(s); SD, standard deviation; BMP-7, bone morphogenetic protein-7; G1, patients who were treated with transplantation of autologous bone graft; G2, patients who were treated with additional application of BMP-7.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036623&req=5

f2-jir-9-155: Evaluation of the expression pattern of VEGF after nonunion treatment.Notes: (A) Serum concentrations of VEGF in pg/mL 1d before and 2d, 1w, 2w, 4w, 6w, and 12w after surgery. Significant differences are indicated by a star (P<0.05, whiskers are SD). (B) Box plot after 2d to 2w of surgery. Whiskers demonstrate one-quarter of the sample. Stars indicate significant differences comparing the study and control groups at the time point (P<0.05).Abbreviations: VEGF, vascular endothelial growth factor; p, preoperative; d, day(s); w, week(s); SD, standard deviation; BMP-7, bone morphogenetic protein-7; G1, patients who were treated with transplantation of autologous bone graft; G2, patients who were treated with additional application of BMP-7.
Mentions: Significant differences in angiogenesis potential (VEGF serum levels) could be found in the first days after surgery comparing G2 and the control groups. In detail, the VEGF serum levels in the BMP-7 group rose from day 2 after surgery to a peak on day 14 and were finally comparable to those at admission 4 weeks after surgery (Figure 2A). In contrast, the VEGF serum levels in our control group decreased after surgery on day 2 after surgery and afterward showed a VEGF time course that was comparable to the G2 group, but in contrast to this, the absolute serum levels of VEGF showed significant differences before surgical treatment (P=0.035) and on day 2 after surgery (P=0.009) comparing the study group and control group. Furthermore, the absolute increase in the VEGF serum levels between preoperative values and values at week 2 was considerably higher in the G2 group compared to the control group (absolute increase 2 weeks vs preoperative: G2, 186.60 pg/mL and G1, 100.53 pg/mL). In summary, the increase (Figure 2B) and absolute amount of VEGF levels in the BMP-7 group were considerably higher than in the control group during the first 2 weeks after surgery (G2 after 2 weeks: 351.95 pg/mL; G1 after 2 weeks: 191.57 pg/mL) as shown in Figure 2.

View Article: PubMed Central - PubMed

ABSTRACT

The local application of bone morphogenetic protein-7 (BMP-7) in combination with the transplantation of autologous bone graft improves the outcome in nonunion treatment; however, the specific reasons remain unclear. In this study, we sought to determine if the local application of BMP-7 contributes to improved bone regeneration in nonunion therapy by modulation of the angiogenic and inflammable cytokine expression patterns of the early inflammation response. Therefore, we utilized the analysis of serological cytokine expression patterns. As a matched pair analysis, best-fitting patients who were treated with transplantation of autologous bone graft (G1, n=10) were compared with patients who were treated with additional application of BMP-7 (G2, n=10). The changes in the cytokine expression patterns were monitored and correlated to clinical data of bone healing. Significant differences in angiogenesis potential (vascular endothelial growth factor [VEGF] serum levels) could be found in the first days after surgery (P&lt;0.05). Furthermore, the increase and absolute amount of VEGF levels in the BMP-7 group were considerably higher than in the control group during the first 2 weeks after surgery. The expression pattern of inflammable cytokines showed noticeable differences in the time point of significant elevated levels, in particular, inflammable cytokines showed an earlier peak in G2. Furthermore, interleukin-6 was significantly elevated within the first week only, comparing G2 to G1 (P&lt;0.05). Our findings indicate that BMP-7 induces an early and more intense expression of VEGF via a direct and postulated indirect pathway, thereby providing a favorable environment for bone healing. Moreover, application of BMP-7 leads to an earlier expression of known proinflammatory cytokines. The results of this study show that application of BMP-7 leads to costimulatory effect on both angiogenic and inflammable cytokine expression patterns that may serve as a possible stimulus for bone regeneration.

No MeSH data available.


Related in: MedlinePlus