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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.


Related in: MedlinePlus

Evaluation of the expression pattern of IL-6 after nonunion treatment.Notes: (A) Serum concentrations of IL-6 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 SEM). (B) Box plot in a logarithmic scale on the y-axis of day before to 1w after surgery. Whiskers demonstrate one-quarter of the sample. Stars indicate significant differences comparing the study and control group at the time point (P<0.05).Abbreviations: IL-6, interleukin-6; p, preoperative; d, day(s); w, week(s); SEM, standard error of the mean; 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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f4-jir-9-155: Evaluation of the expression pattern of IL-6 after nonunion treatment.Notes: (A) Serum concentrations of IL-6 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 SEM). (B) Box plot in a logarithmic scale on the y-axis of day before to 1w after surgery. Whiskers demonstrate one-quarter of the sample. Stars indicate significant differences comparing the study and control group at the time point (P<0.05).Abbreviations: IL-6, interleukin-6; p, preoperative; d, day(s); w, week(s); SEM, standard error of the mean; 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: IL-6 was significantly elevated within the first week only, comparing G2 group to the G1 group. In detail, the IL-6 levels in the BMP-7 group increased to a peak mean concentration 2 days after surgery. Afterward, IL-6 plasma values decreased to similar levels at admission (4.9±1.0 pg/mL) within the first 2 weeks after surgical therapy (Figure 4A). Compared to this, in the control group, the levels of IL-6 at admission were similar to those in the G2 group. Furthermore, the IL-6 serum levels in the control group after 1 week of surgery were similar (6.1±3.0 pg/mL) to those at admission or to those in the BMP-7 group after 2 weeks of surgery. However in contrast, the peak value on day 2 was significantly lower (9.1±3.0 pg/mL) in the control group than any other value in the BMP-7 group within the first week after surgery. Additionally, during the following time course, a constant decrease was observed within a minimum 6 weeks after surgery (1.6±0.8 pg/mL, P=0.014 compared to the BMP-7 group). Additionally, the absolute increase on day 2 compared to the admission level was higher in the BMP-7 group (absolute increase: 59.2 pg/mL) than in the control group (absolute increase: 7.1 pg/mL; Figure 4B). This increase and peak value is significant on day 2 comparing both study groups (P=0.049), suggesting an increased process of inflammation in the BMP-7 group.


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 IL-6 after nonunion treatment.Notes: (A) Serum concentrations of IL-6 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 SEM). (B) Box plot in a logarithmic scale on the y-axis of day before to 1w after surgery. Whiskers demonstrate one-quarter of the sample. Stars indicate significant differences comparing the study and control group at the time point (P<0.05).Abbreviations: IL-6, interleukin-6; p, preoperative; d, day(s); w, week(s); SEM, standard error of the mean; 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.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5036623&req=5

f4-jir-9-155: Evaluation of the expression pattern of IL-6 after nonunion treatment.Notes: (A) Serum concentrations of IL-6 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 SEM). (B) Box plot in a logarithmic scale on the y-axis of day before to 1w after surgery. Whiskers demonstrate one-quarter of the sample. Stars indicate significant differences comparing the study and control group at the time point (P<0.05).Abbreviations: IL-6, interleukin-6; p, preoperative; d, day(s); w, week(s); SEM, standard error of the mean; 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: IL-6 was significantly elevated within the first week only, comparing G2 group to the G1 group. In detail, the IL-6 levels in the BMP-7 group increased to a peak mean concentration 2 days after surgery. Afterward, IL-6 plasma values decreased to similar levels at admission (4.9±1.0 pg/mL) within the first 2 weeks after surgical therapy (Figure 4A). Compared to this, in the control group, the levels of IL-6 at admission were similar to those in the G2 group. Furthermore, the IL-6 serum levels in the control group after 1 week of surgery were similar (6.1±3.0 pg/mL) to those at admission or to those in the BMP-7 group after 2 weeks of surgery. However in contrast, the peak value on day 2 was significantly lower (9.1±3.0 pg/mL) in the control group than any other value in the BMP-7 group within the first week after surgery. Additionally, during the following time course, a constant decrease was observed within a minimum 6 weeks after surgery (1.6±0.8 pg/mL, P=0.014 compared to the BMP-7 group). Additionally, the absolute increase on day 2 compared to the admission level was higher in the BMP-7 group (absolute increase: 59.2 pg/mL) than in the control group (absolute increase: 7.1 pg/mL; Figure 4B). This increase and peak value is significant on day 2 comparing both study groups (P=0.049), suggesting an increased process of inflammation in the BMP-7 group.

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