BMP-7-induced ectopic bone formation and fracture healing is impaired by systemic NSAID application in C57BL/6-mice.
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BMP-7-induced ectopic bone formation and fracture healing is impaired by systemic NSAID application in C57BL/6-mice. / Spiro, Alexander Simon; Beil, Frank Timo; Baranowsky, Anke; Barvencik, Florian; Schilling, Arndt; Nguyen, Khoa; Khadem, Shahram; Seitz, Sebastian; Rueger, Johannes Maria; Schinke, Thorsten; Amling, Michael.
in: J ORTHOP RES, Jahrgang 28, Nr. 6, 6, 2010, S. 785-791.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - BMP-7-induced ectopic bone formation and fracture healing is impaired by systemic NSAID application in C57BL/6-mice.
AU - Spiro, Alexander Simon
AU - Beil, Frank Timo
AU - Baranowsky, Anke
AU - Barvencik, Florian
AU - Schilling, Arndt
AU - Nguyen, Khoa
AU - Khadem, Shahram
AU - Seitz, Sebastian
AU - Rueger, Johannes Maria
AU - Schinke, Thorsten
AU - Amling, Michael
PY - 2010
Y1 - 2010
N2 - Nonsteroidal antiinflammatory drugs (NSAIDs) are known to potentially impair the fracture healing process. The aim of the present study was to determine if the impairment of bone healing by systemic NSAID application is, at least in part, due to an interaction of NSAIDs with the bone anabolic BMP-7 pathway. Therefore, we first analyzed fracture healing in control and diclofenac-treated mice, where we not only found a significant impairment of fracture healing due to diclofenac treatment as assessed by biomechanical testing and microCT imaging, but also found high coexpression of bone morphogenetic protein-7 (BMP-7) and cyclooxygenase-2 (COX-2) within the fracture callus of both groups. To experimentally address the possible interaction between BMP-7 and COX-2, we then induced ectopic bone formation in control (n = 10) and diclofenac-treated mice (n = 10) by application of BMP-7 (recombinant human OP-1, rhOP-1) into the hamstring muscles. After 20 days of treatment, each ectopic bone nodule was analyzed by contact-radiography, microCT, histology, and histomorphometry. Diclofenac application decreased the trabecular number and bone mass in the ectopic bone nodules significantly due to reduced osteoblast number and activity. These data demonstrate that the bone anabolic effect of BMP-7 and fracture healing is impaired by diclofenac application, and suggest that the potential negative impact of NSAIDs on fracture healing is, at least in part, due to interference with BMP-7 signaling. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
AB - Nonsteroidal antiinflammatory drugs (NSAIDs) are known to potentially impair the fracture healing process. The aim of the present study was to determine if the impairment of bone healing by systemic NSAID application is, at least in part, due to an interaction of NSAIDs with the bone anabolic BMP-7 pathway. Therefore, we first analyzed fracture healing in control and diclofenac-treated mice, where we not only found a significant impairment of fracture healing due to diclofenac treatment as assessed by biomechanical testing and microCT imaging, but also found high coexpression of bone morphogenetic protein-7 (BMP-7) and cyclooxygenase-2 (COX-2) within the fracture callus of both groups. To experimentally address the possible interaction between BMP-7 and COX-2, we then induced ectopic bone formation in control (n = 10) and diclofenac-treated mice (n = 10) by application of BMP-7 (recombinant human OP-1, rhOP-1) into the hamstring muscles. After 20 days of treatment, each ectopic bone nodule was analyzed by contact-radiography, microCT, histology, and histomorphometry. Diclofenac application decreased the trabecular number and bone mass in the ectopic bone nodules significantly due to reduced osteoblast number and activity. These data demonstrate that the bone anabolic effect of BMP-7 and fracture healing is impaired by diclofenac application, and suggest that the potential negative impact of NSAIDs on fracture healing is, at least in part, due to interference with BMP-7 signaling. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
M3 - SCORING: Zeitschriftenaufsatz
VL - 28
SP - 785
EP - 791
JO - J ORTHOP RES
JF - J ORTHOP RES
SN - 0736-0266
IS - 6
M1 - 6
ER -