title: Intradiscal injections of osteogenic protein-1 restore the viscoelastic properties of degenerated intervertebral discs.
abstract: BACKGROUND
  Using biochemical, histological, and radiological parameters in a rabbit model of intervertebral disc (IVD) degeneration, the intradiscal injection of a growth factor, such as osteogenic protein-1 (OP-1), has been shown to regenerate the IVD. However, very little is known about how such a biological therapeutic approach affects the biomechanical properties of the degenerated IVD.
  
  
  OBJECTIVE
  To investigate the effects of an intradiscal injection of OP-1 on the biomechanical properties of IVDs in the rabbit annular-puncture disc degeneration model and to determine their relationship to biochemical properties.
  
  
  METHODS
  In vivo study on the effects of intradiscally administered OP-1 on the biomechanical and biochemical properties of IVDs in the rabbit annular-puncture disc degeneration model.
  
  
  METHODS
  New Zealand White rabbits (n=16) underwent annulus fibrosus (AF) puncture, using an 18-gauge needle, at L2-L3 and L4-L5 (L3-L4: nonpunctured control). Four weeks later, the punctured discs received an injection of either 5% lactose (10 microL) or OP-1 (100 microg/10 microL of 5% lactose) into the nucleus pulposus (NP). The disc height was radiographically monitored biweekly. After sacrifice and removal of bone-disc-bone complexes 8 weeks postinjection, the dynamic viscoelastic properties of the IVDs were tested by applying a cycle of sinusoidal strain in uniaxial compression at six loading frequencies (0.05 to 2 Hz). The biochemical properties of the dissected IVDs were then analyzed and correlated with the biomechanical properties.
  
  
  RESULTS
  A single injection of OP-1 significantly restored disc height when compared with the lactose-injected discs (OP-1 vs. lactose, p<.001). The elastic modulus of the IVDs in the OP-1-injected discs was significantly higher than that in the lactose-injected discs at all frequencies (mean: +43%, p<.001). The viscous modulus in the OP-1-injected discs was significantly higher at 0.05, 0.2, 0.5, and 1 Hz (mean: +55%, p<.001) and showed higher tendencies at other frequencies (p=.08-.09). For both moduli, no significant differences were observed between the OP-1-injected and the nonpunctured control discs. The OP-1 injection significantly increased the proteoglycan (PG) content in the NP and AF, and the collagen content in the NP (p<.001-.05). Both elastic and viscous moduli showed significant positive correlations with PG content in the NP and collagen content in the NP and AF (Rho=.357-.466, p=.010-.047).
  
  
  CONCLUSIONS
  We have shown for the first time that an injection of the growth factor, OP-1, restored the biomechanical properties of IVDs in a rabbit model of IVD degeneration. Comparing biomechanical with biochemical data suggests that the OP-1-induced biomechanical restoration was a consequence of increased activities of anabolic pathways that resulted in biochemical changes in the IVD.
authors.affiliation: Department of Orthopedic Surgery, Rush University Medical Center, 1735 W. Harrison Street, Chicago, IL 60612 USA.
authors.forename: Kei
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Masuda
authors.forename: Jesse G
authors.initials: JG
authors.lastname: Kim
authors.forename: Nozomu
authors.initials: N
authors.lastname: Inoue
authors.forename: Koji
authors.initials: K
authors.lastname: Akeda
authors.forename: Gunnar B J
authors.initials: GB
authors.lastname: Andersson
authors.forename: Howard S
authors.initials: HS
authors.lastname: An
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D004195:Disease Models, Animal; D015552:Injections, Intralesional; D007403:Intervertebral Disc / Q000187:drug effects* / Q000473:pathology*; D011817:Rabbits; D013122:Spinal Diseases / Q000188:drug therapy*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
chemical_list: D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta