title: The treatment of nonunions with application of BMP-7 increases the expression pattern for angiogenic and inflammable cytokines: a matched pair analysis.
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.
authors.affiliation: Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital, HTRG - Heidelberg Trauma Research Group, Heidelberg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Haubruck
authors.affiliation: Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital, HTRG - Heidelberg Trauma Research Group, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kammerer
authors.affiliation: Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital, HTRG - Heidelberg Trauma Research Group, Heidelberg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Korff
authors.affiliation: Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital, HTRG - Heidelberg Trauma Research Group, Heidelberg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Apitz
authors.affiliation: Department of Orthopedics Wuhan, Wuhan Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xiao
authors.affiliation: Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital, HTRG - Heidelberg Trauma Research Group, Heidelberg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Büchler
authors.affiliation: Department of Paraplegiology, Berufsgenossenschaftliche Unfallklinik Ludwigshafen, Ludwigshafen.
authors.forename: Bahram
authors.initials: B
authors.lastname: Biglari
authors.affiliation: Department for Trauma Surgery, Theresienkrankenhaus und St. Hedwigs-Klinik GmbH, Mannheim.
authors.forename: Gerald
authors.initials: G
authors.lastname: Zimmermann
authors.affiliation: Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Daniel
authors.affiliation: Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital, HTRG - Heidelberg Trauma Research Group, Heidelberg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schmidmaier
authors.affiliation: Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital, HTRG - Heidelberg Trauma Research Group, Heidelberg, Germany.
authors.forename: Arash
authors.initials: A
authors.lastname: Moghaddam
keywords: IL-6; VEGF; angiogenesis; bone regeneration; cytokines; inflammation