title: Restoration of disc height loss by recombinant human osteogenic protein-1 injection into intervertebral discs undergoing degeneration induced by an intradiscal injection of chondroitinase ABC.
abstract: METHODS
  In vivo study of the effect of an injection of recombinant human osteogenic protein-1 into degenerated discs induced by chondroitinase ABC.
  
  
  OBJECTIVE
  To investigate the efficacy of an injection of recombinant human osteogenic protein-1 to induce the recovery of disc height, and biochemical and histologic repair, in discs degenerated through enzymatic digestion by chondroitinase ABC.
  
  
  BACKGROUND
  Chondroitinase ABC is currently proposed as a chemonucleolysis agent; however, postchemonucleolysis degeneration is currently unavoidable. Recombinant human OP-1 has been shown to promote extracellular matrix repair in vitro and in vivo.
  
  
  METHODS
  Fifty-four adolescent New Zealand white rabbits were used. Four weeks after an initial injection of chondroitinase ABC (10 mU/disc), 5% lactose (10 microL/disc) or recombinant human osteogenic protein-1 (100 microg in 10 microL lactose/disc) was injected. Disc heights were monitored radiographically at 2-week intervals, and rabbits were killed at 6, 8, 12, and 16 weeks after the initial chondroitinase ABC injections. The intervertebral discs were subjected to histologic and biochemical analyses.
  
  
  RESULTS
  Significant disc space narrowing was observed in both groups 2 weeks after the injection of chondroitinase ABC. In the chondroitinase ABC/lactose group, this narrowing progressed after the vehicle injection and was sustained for up to 16 weeks. In the chondroitinase ABC/recombinant human osteogenic protein-1 group, the disc height index showed a significant increase at 6 weeks (lactose vs. recombinant human osteogenic protein-1; P < 0.01); this recovery was sustained for up to 16 weeks. The proteoglycan content was higher in the chondroitinase ABC/recombinant human osteogenic protein-1 group than in the chondroitinase ABC/lactose group. However, histologic changes, after the recombinant human osteogenic protein-1 injection, were not observed.
  
  
  CONCLUSIONS
  A single injection of recombinant human osteogenic protein-1 into a rabbit disc dramatically reversed the decrease in disc height induced by chondroitinase ABC chemonucleolysis. The recovery was significant and sustained over the next 12 weeks. The therapeutic effects of both chondroitinase ABC chemonucleolysis and recombinant human osteogenic protein-1 injections should be further explored in higher animals before it is applied to humans.
authors.affiliation: Department of Orthopedic Surgery, Rush Medical College at Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Imai
authors.forename: Masahiko
authors.initials: M
authors.lastname: Okuma
authors.forename: Howard S
authors.initials: HS
authors.lastname: An
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Michiaki
authors.initials: M
authors.lastname: Yamada
authors.forename: Carol
authors.initials: C
authors.lastname: Muehleman
authors.forename: Eugene
authors.initials: E
authors.lastname: Thonar
authors.forename: Koichi
authors.initials: K
authors.lastname: Masuda
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000235:genetics; D019765:Chondroitin ABC Lyase / Q000008:administration & dosage / Q000009:adverse effects*; D005240:Feasibility Studies; D006801:Humans; D007278:Injections, Spinal; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007404:Intervertebral Disc Chemolysis; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage; D013122:Spinal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; D019765:Chondroitin ABC Lyase