BMP‐7–induced ectopic bone formation and fracture healing is impaired by systemic NSAID application in C57BL/6‐mice
Open Access
- 14 April 2010
- journal article
- research article
- Published by Wiley in Journal of Orthopaedic Research
- Vol. 28 (6), 785-791
- https://doi.org/10.1002/jor.21044
Abstract
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 µCT 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, µCT, 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. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:785–791, 2010This publication has 37 references indexed in Scilit:
- Bone formation following OP‐1 implantation is improved by addition of autogenous bone marrow cells in a canine femur defect modelJournal of Orthopaedic Research, 2007
- Clinical applications of BMP-7/OP-1 in fractures, nonunions and spinal fusionInternational Orthopaedics, 2007
- Effects of local infusion of OP‐1 on particle‐induced and NSAID‐induced inhibition of bone ingrowth in vivoJournal of Biomedical Materials Research Part A, 2006
- Ectopic bone formation using osteogenic protein-1 carried by a solution precipitated hydroxyapatiteJournal of Biomedical Materials Research, 2004
- Regulation of bone morphogenetic protein‐2 expression by endogenous prostaglandin E2 in human mesenchymal stem cellsJournal of Cellular Physiology, 2004
- Bone Morphogenetic Protein 2 Induces Cyclo-oxygenase 2 in Osteoblasts via a Cbfa1 Binding Site: Role in Effects of Bone Morphogenetic Protein 2 In Vitro and In VivoJournal of Bone and Mineral Research, 2002
- Healing Course of Primate Ulna Segmental Defects Treated With Osteogenic Protein-1Journal of Investigative Surgery, 2002
- Bone Morphogenetic Protein-2 Enhances Osteoclast Formation Mediated by Interleukin-1α through Upregulation of Osteoclast Differentiation Factor and Cyclooxygenase-2Biochemical and Biophysical Research Communications, 1999
- Complete Regeneration of Bone in the Baboon by Recombinant Human Osteogenic Protein-1 (hOP-1, Bone Morphogenetic Protein-7)Growth Factors, 1996
- Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committeeJournal of Bone and Mineral Research, 1987