Effects of Diclofenac Sodium on BMP-induced Inflammation in a Rodent Model.

Abstract

STUDY DESIGN:

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.

SUMMARY OF BACKGROUND DATA:

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.

CONCLUSION:

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.

LEVEL OF EVIDENCE:

N/A.

• Authors: Shuai Ye, Jong-Han Yim, Jung-Ryul Kim, Kyu Yun Jang, Hongen Wang, Jeffrey C Wang, Kwang-Bok Lee
• Journal: Spine (Spine (Phila Pa 1976)) Vol. 40 Issue 14 Pg. E799-807 (Jul 15 2015) ISSN: 1528-1159 [Electronic] United States
• PMID: 26164161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Bone Morphogenetic Protein 2
• Cytokines
• Drug Implants
• Recombinant Proteins
• Transforming Growth Factor beta
• recombinant human bone morphogenetic protein-2
• Diclofenac

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, therapeutic use)
• Back (surgery)
• Bone Morphogenetic Protein 2 (administration & dosage, adverse effects, pharmacology)
• Cytokines (blood)
• Diclofenac (administration & dosage, therapeutic use)
• Drug Implants (administration & dosage, therapeutic use)
• Edema (pathology)
• Inflammation (chemically induced, drug therapy, pathology, physiopathology)
• Magnetic Resonance Imaging
• Male
• Osteogenesis
• Porifera
• Prospective Studies
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (administration & dosage, adverse effects, pharmacology)
• Transforming Growth Factor beta (administration & dosage, adverse effects, pharmacology)