Nitric oxide modulates recombinant human bone morphogenetic protein-2-induced corticocancellous autograft incorporation: a study in rat intertransverse fusion. Academic Article uri icon

Overview

abstract

  • A novel rat model was used to investigate the effect of nitric oxide synthase inhibition in posterior spinal fusion augmented with recombinant human bone morphogenetic protein-2. Nitric oxide (NO) has important physiological functions including the modulation of fracture healing. Recombinant human BMP-2 (rhBMP-2) enhances spinal fusion. It is not known whether nitric oxide has a role in rhBMP-2 enhanced spinal fusion and remodeling. A novel rat intertransverse fusion model was created using a defined volume of bone graft along with a collagen sponge carrier, which was compacted and delivered using a custom jig. The control groups consisted of a sham group (S, n = 20), an autograft + carrier group (A, n = 28) and a group consisting of 43 microg of rhBMP-2 mixed with autograft + carrier (AB, n = 28). Two experimental groups received a nitric oxide synthase (NOS) inhibitor, N (G)-nitro L-arginine methyl ester, in a dose of 1 mg/ml ad lib in the drinking water (AL, n = 28) and one of these experimental groups had rhBMP-2 added to the graft mixture at the time of surgery (ALB, n = 28). Rats were killed at 22 and 44 days, spinal columns subjected to radiology, biomechanics and histology. On a radiographic score (0-4) indicating progressive maturation of bone fusion mass, no difference was found between the A and AL groups, however, there was a significant enhancement of fusion when rhBMP-2 was added when compared to the A group (P < 0.001). However, on day 44, the ALB group showed significantly less fusion progression when compared to the AB group (P < 0.01). There was a 25% (P < 0.05) more fusion-mass-area in day 44 of ALB group when compared to day 44 of the AB group indicating that NOS inhibition delayed the remodeling of the fusion mass. Biomechanically, the rhBMP-2 groups were stiffer at all time points compared to the NOS inhibited groups. Decalcified histology demonstrated that there was a delay in graft incorporation whenever NOS was inhibited (AL and ALB groups) as assessed by a 5 point histological maturation score. In a novel model of rat intertransverse process fusion, nitric oxide synthase modulates rhBMP-2 induced corticocancellous autograft incorporation.

publication date

  • January 9, 2010

Research

keywords

  • Bone Morphogenetic Protein 2
  • Bone Transplantation
  • Nitric Oxide
  • Osteogenesis
  • Recombinant Fusion Proteins
  • Spinal Fusion
  • Transplantation, Autologous

Identity

PubMed Central ID

  • PMC2899991

Scopus Document Identifier

  • 77954533528

Digital Object Identifier (DOI)

  • 10.1002/jcb.10527

PubMed ID

  • 20063019

Additional Document Info

volume

  • 19

issue

  • 6