title: Effects of Diclofenac Sodium on BMP-induced Inflammation in a Rodent Model.
abstract: METHODS
  Prospective in vivo rodent model of bone morphogenetic protein (BMP)-induced inflammation.
  
  
  OBJECTIVE
  To evaluate the effects of the coadministration of the nonsteroidal anti-inflammatory drug, diclofenac, on BMP-induced inflammation using our rodent model.
  
  
  BACKGROUND
  The use of BMP-2 is associated with inflammation in the neck and back. We have previously reported on a rodent model of BMP-2-induced inflammation.
  
  
  METHODS
  Seven treatment groups were: Surgery alone; absorbable collagen sponges (ACS) alone; 20 μg rhBMP-2 on ACS with no diclofenac; 20 μg rhBMP-2 on ACS+50 mg diclofenac injections; 20 μg rhBMP-2 on ACS+75 mg diclofenac; 20 μg rhBMP-2 on ACS+100 mg diclofenac; and 20 μg rhBMP-2 on ACS+125 mg diclofenac. Using magnetic resonance imaging, inflammation (soft tissue edema volume) was assessed at 3 hours and at 2, 7, and 14 days after implantation. Western blot analysis, histology, and immunohistochemical staining were performed to compare the inflammatory response between groups. The mass size and tissue density of bone formation were compared between groups using plain radiography.
  
  
  RESULTS
  Soft-tissue edema volumes in all diclofenac-treated groups were significantly lower than those observed in the rhBMP-2 alone. There was no significant difference in soft tissue edema volumes between 4 diclofenac-treated groups. The expression of NF-κB signaling pathway related proteins (p65 and p-p65) were increased in the rhBMP-2+ACS group and decreased in diclofenac treatment groups. Histological findings and immunohistochemical staining were consistent with the Western blot results. There was no significant difference between the rhBMP-2+ACS group and diclofenac treatment groups in terms of the mass size and tissue density of bone formation.
  
  
  CONCLUSIONS
  Coadministration of diclofenac sodium can reduce the inflammatory response to BMP-2 without impairing heterotopic bone formation in our rodent model of BMP-2-induced inflammation.
  
  
  METHODS
  N/A.
authors.affiliation: *Departments of Orthopaedic Surgery †Pathology ‡Internal Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea; and §Department of Orthopaedic Surgery, University of Southern California, Los Angeles, CA.
authors.forename: Shuai
authors.initials: S
authors.lastname: Ye
authors.forename: Jong-Han
authors.initials: JH
authors.lastname: Yim
authors.forename: Jung-Ryul
authors.initials: JR
authors.lastname: Kim
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Hongen
authors.initials: H
authors.lastname: Wang
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Wang
authors.forename: Kwang-Bok
authors.initials: KB
authors.lastname: Lee
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001415:Back / Q000601:surgery; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D004008:Diclofenac / Q000008:administration & dosage / Q000627:therapeutic use*; D004343:Drug Implants / Q000008:administration & dosage / Q000627:therapeutic use; D004487:Edema / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D010012:Osteogenesis; D011161:Porifera; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D055396:Bone Morphogenetic Protein 2; D016207:Cytokines; D004343:Drug Implants; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D004008:Diclofenac