title: Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits.
abstract: METHODS
  A study of the disc height and biochemical changes in the rabbit intervertebral disc after injection of osteogenic protein-1 into the nucleus pulposus.
  
  
  OBJECTIVE
  To evaluate the in vivo effects of osteogenic protein-1 administered intradiscally to the intervertebral disc of rabbits.
  
  
  BACKGROUND
  Growth factors, such as osteogenic protein-1 and transforming growth factor-beta, have the ability to stimulate synthesis of proteoglycan and collagen in vitro. No attempts have yet been made to determine the effects of these growth factors in an in vivo model.
  
  
  METHODS
  Twenty-four New Zealand adolescent white rabbits were divided evenly into two subject groups. In one group, three consecutive intervertebral discs were injected with saline; whereas in the other group, they were injected with osteogenic protein-1 in saline. At 2, 4, and 8 weeks after the injection, the intervertebral disc heights of the injected specimens were measured by lateral plain radiographs and compared with preinjection measurements. The change in disc height was expressed as the percent disc height index compared with the preinjection value. After the radiographic measurements were obtained, the intervertebral discs were removed and analyzed for DNA, proteoglycan, and collagen contents.
  
  
  RESULTS
  At 2 weeks after the injections, the mean disc height index of the osteogenic protein-1-injected discs was 15% greater than that of the saline group. The increase in disc height with osteogenic protein-1 injection was still statistically significant at the 4- and 8-week time points. The proteoglycan content of the nucleus pulposus in discs injected with osteogenic protein-1 was higher than that in the saline group at the 2-week time point. The osteogenic protein-1-induced effect on the proteoglycan content was also present at the 4- and 8- week time intervals; however, these increases were not statistically significant. There were no significant differences in the DNA content, normalized to noninjected control, of the nucleus pulposus between the saline and osteogenic protein-1 groups. However, a significant increase in the DNA content of the anulus fibrosus in the osteogenic protein-1 group, compared with that of the anulus fibrosus in the saline group, was observed after 4 weeks.
  
  
  CONCLUSIONS
  To date, no study has demonstrated the potential in vivo effects of growth factors on the intervertebral disc. The present study reports that the intradiscal administration of osteogenic protein-1 in vivo results in an increased disc height present at 2, 4, and 8 weeks and an increase in PG content of the nucleus pulposus at the 2-week time point. Therefore, osteogenic protein-1 may act to stimulate metabolic activity in the nucleus pulposus. Continued research is needed to evaluate the potential of growth factor-induced reversal of age-related disc degeneration in an appropriate animal model. In addition, studies in a nonhuman primate animal model will be essential before considering intradiscal injection of growth factors in humans.
authors.affiliation: Department of Orthopedic Surgery, Rush Medical College at Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Howard S
authors.initials: HS
authors.lastname: An
authors.forename: Kenji
authors.initials: K
authors.lastname: Takegami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamada
authors.forename: Cahn M
authors.initials: CM
authors.lastname: Nguyen
authors.forename: Eugene J-M A
authors.initials: EJ
authors.lastname: Thonar
authors.forename: Kern
authors.initials: K
authors.lastname: Singh
authors.forename: Gunnar B
authors.initials: GB
authors.lastname: Andersson
authors.forename: Koichi
authors.initials: K
authors.lastname: Masuda
mesh_terms: D000367:Age Factors; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000032:analysis; D007267:Injections; D007403:Intervertebral Disc / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D008159:Lumbar Vertebrae; D011509:Proteoglycans / Q000378:metabolism*; D011817:Rabbits; D011859:Radiography; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014867:Water / Q000378:metabolism
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D014867:Water; D003094:Collagen; D004247:DNA