BACKGROUND CONTEXT: 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. PURPOSE: 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. STUDY DESIGN/ SETTING: 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.
BACKGROUND CONTEXT: 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. PURPOSE: 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. STUDY DESIGN/ SETTING: 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: Svenja Illien-Jünger; Young Lu; Devina Purmessur; Jillian E Mayer; Benjamin A Walter; Peter J Roughley; Sheeraz A Qureshi; Andrew C Hecht; James C Iatridis Journal: Spine J Date: 2014-04-24 Impact factor: 4.166