title: The effect of bone morphogenetic protein-2 injection at different time points on intervertebral disk degeneration in a rat tail model.
abstract: METHODS
  Prospective in vivo rat tail model of disk degeneration comparing the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) injection over various time points and grades of degeneration.
  
  
  OBJECTIVE
  To evaluate the effect of timing and disk grade on rhBMP-2 injection in a rat tail model of disk degeneration.
  
  
  BACKGROUND
  rhBMP-2 stimulates the proliferation of intervertebral disk cells and the secretion of extracellular matrix. However, few in vivo studies have demonstrated whether rhBMP-2 also improves disk degeneration and the severity of disk degeneration beyond which disks cannot be recovered by rhBMP-2 treatment.
  
  
  METHODS
  Two coccygeal disks of each rodent subject were punctured percutaneously using an 18 G needle. At 4 weeks after the puncture, disks demonstrating induced degeneration were divided into 3 groups. Groups 1, 2, and 3 were treated with 7.5 μg rhBMP-2 or phosphate buffered saline by injection into the disk at 4, 6, and 8 weeks postpuncture, respectively. Plain radiographs and magnetic resonance images (MRIs) were obtained on the day of puncture and every 2 weeks thereafter until sacrifice. At 6 weeks after injection, each group was killed and examined with histologic and immunohistochemical analysis.
  
  
  RESULTS
  According to MRI disk grade evaluation of the degenerative disk, rhBMP-2 significantly improved degeneration grade in group 1 at 2 weeks after injection. According to radiographic disk height index, groups 1 and 2 showed a trend toward improvement at 2 weeks after rhBMP-2 injection. Chondrogenic differentiation was noted on immunohistochemical staining of many disks treated with rhBMP-2.
  
  
  CONCLUSIONS
  rhBMP-2 injection of degenerated disks at 4 weeks postpuncture induced a transient improvement in disk grade on MRI and stimulated chondrogenic differentiation. These data suggest rhBMP-2 as a potential therapy for degenerative disk disease.
authors.affiliation: Department of Orthopaedic Surgery, University of California at Los Angeles (UCLA), Los Angeles, CA.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Inoue
authors.forename: Scott R
authors.initials: SR
authors.lastname: Montgomery
authors.forename: Bayan
authors.initials: B
authors.lastname: Aghdasi
authors.forename: Tuncay
authors.initials: T
authors.lastname: Kaner
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Tan
authors.forename: Haijun
authors.initials: H
authors.lastname: Tian
authors.forename: Rodney
authors.initials: R
authors.lastname: Terrell
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Wang
authors.forename: Michael D
authors.initials: MD
authors.lastname: Daubs
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D007267:Injections; D007403:Intervertebral Disc / Q000187:drug effects / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D011446:Prospective Studies; D011509:Proteoglycans / Q000378:metabolism; D011677:Punctures; D011859:Radiography; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013194:Staining and Labeling; D013623:Tail / Q000187:drug effects*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D055396:Bone Morphogenetic Protein 2; D011509:Proteoglycans; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2