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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.


A timeline of the protocol for taking blood samples throughout this study.Notes: Blood was drained from each patient 1d p and 2d, 1w, 2w, 4w, 6w, and 12w after surgery.Abbreviations: p, preoperative; d, day(s); w, week(s).
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f1-jir-9-155: A timeline of the protocol for taking blood samples throughout this study.Notes: Blood was drained from each patient 1d p and 2d, 1w, 2w, 4w, 6w, and 12w after surgery.Abbreviations: p, preoperative; d, day(s); w, week(s).

Mentions: First blood samples were taken during the preoperative examination. Additional samples were taken postoperatively at standardized intervals, on days 2 and 7 and on 1, 2, 4, 6, and 12 weeks after surgery (Figure 1). The samples were collected between 8 am and 11 am. In all, 3×7.5 mL serum samples (S-Monovette 7.5 mL; Sarstedt AG & Co., Nümbrecht, Germany) and 1×9 mL ethylenediaminetetraacetic acid were taken, centrifuged, aliquoted into Eppendorf tubes and stored at −80°C. Furthermore, C reactive protein (CRP) and leukocyte serum values were assessed during our clinical routine in the first 2 weeks to analyze systemic inflammation. Herewith, we assessed if application of BMP-7 and autologous cancellous bone graft influences systemic CRP and leukocyte levels and thereby a systemic unspecific inflammation that might modulate the cytokine serum values. Furthermore, a possible bias by infection or postoperative ongoing elevated CRP and leukocyte blood levels could be detected. Luminex Performance Human High Sensitivity Assays (Quantikine®,; R&D Systems, Inc., Minneapolis, MN, USA) were used to measure the cytokine serum levels of VEGF, TNF-α, IL-1, IL-6, IL-8, and IL-10 as described in the factory manual. The lab technician performing the Luminex assays was blinded to patient data and kept to manufacturer’s instructions during the measurements.


The treatment of nonunions with application of BMP-7 increases the expression pattern for angiogenic and inflammable cytokines: a matched pair analysis
A timeline of the protocol for taking blood samples throughout this study.Notes: Blood was drained from each patient 1d p and 2d, 1w, 2w, 4w, 6w, and 12w after surgery.Abbreviations: p, preoperative; d, day(s); w, week(s).
© Copyright Policy
Related In: Results  -  Collection

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

f1-jir-9-155: A timeline of the protocol for taking blood samples throughout this study.Notes: Blood was drained from each patient 1d p and 2d, 1w, 2w, 4w, 6w, and 12w after surgery.Abbreviations: p, preoperative; d, day(s); w, week(s).
Mentions: First blood samples were taken during the preoperative examination. Additional samples were taken postoperatively at standardized intervals, on days 2 and 7 and on 1, 2, 4, 6, and 12 weeks after surgery (Figure 1). The samples were collected between 8 am and 11 am. In all, 3×7.5 mL serum samples (S-Monovette 7.5 mL; Sarstedt AG & Co., Nümbrecht, Germany) and 1×9 mL ethylenediaminetetraacetic acid were taken, centrifuged, aliquoted into Eppendorf tubes and stored at −80°C. Furthermore, C reactive protein (CRP) and leukocyte serum values were assessed during our clinical routine in the first 2 weeks to analyze systemic inflammation. Herewith, we assessed if application of BMP-7 and autologous cancellous bone graft influences systemic CRP and leukocyte levels and thereby a systemic unspecific inflammation that might modulate the cytokine serum values. Furthermore, a possible bias by infection or postoperative ongoing elevated CRP and leukocyte blood levels could be detected. Luminex Performance Human High Sensitivity Assays (Quantikine®,; R&D Systems, Inc., Minneapolis, MN, USA) were used to measure the cytokine serum levels of VEGF, TNF-α, IL-1, IL-6, IL-8, and IL-10 as described in the factory manual. The lab technician performing the Luminex assays was blinded to patient data and kept to manufacturer’s instructions during the measurements.

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.