BMP induced inflammation: a comparison of rhBMP-7 and rhBMP-2

J Orthop Res. 2012 Dec;30(12):1985-94. doi: 10.1002/jor.22160. Epub 2012 Jun 1.

Abstract

Concern has been raised because of reports of inflammatory swelling following the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human bone morphogenetic protein-7 (rhBMP-7). The purpose of this study is to compare the inflammatory action of rhBMP-7 with those of rhBMP-2. ELISA assays (IL-6, TNF-α) were used to measure the cytokine response to different concentrations of rhBMP-7 and -2. Recombinant human BMP-7 was absorbed into absorbable collagen sponges and different amounts were implanted either subcutaneously (SC) or intramuscularly (IM) into the backs of rats. Using MRI and MIPAV software, we measured the degree of soft tissue edema at 3 h and at 2, 4, and 7 days postoperatively. After sacrificing rats on day 7 the inflammatory zone and mass were measured and the tissue examined histologically. Soft tissue edema after rhBMP-7 and rhBMP-2 implantation was dose-dependent and peaked at 3 h for the subcutaneous implants and at 2 days for the intramuscular implants. RhBMP-7 was associated with a significantly smaller soft tissue edema volume than was rhBMP-2 only at the highest dose (20 µg/ml). Both rhBMP-2 and rhBMP-7 triggered dose-dependent inflammatory reactions. Compared to rhBMP-2, rhBMP-7 is associated with somewhat smaller soft tissue edema volumes. Although rhBMP-7 is associated with an inflammatory reaction leading to soft tissue edema, at high doses this response is significantly less than that seen with rhBMP-2. Our animal model can be used to test materials that could ameliorate this reaction.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / metabolism*
  • Bone Morphogenetic Protein 7 / metabolism*
  • Cell Line
  • Cytokines / metabolism
  • Edema / pathology*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Granuloma / metabolism
  • Humans
  • Inflammation / metabolism*
  • Injections, Intramuscular
  • Injections, Subcutaneous
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / metabolism
  • Magnetic Resonance Imaging / methods
  • Male
  • Rats
  • Rats, Inbred Lew
  • Recombinant Proteins / metabolism
  • Time Factors
  • Transforming Growth Factor beta / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • BMP7 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 7
  • Cytokines
  • Interleukin-6
  • Lipopolysaccharides
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • recombinant human bone morphogenetic protein-2