Bone Morphogenetic Protein 13 Reverses Effects of Disc Injury in Animal Model
Introduction: Bone morphogenetic proteins (BMPs) stimulate the growth of skeletal tissues and are approved by the U.S. Food and Drug Administration for use in augmenting spinal fusions. This study investigated whether a recombinant BMP-13 is effective for intervertebral disc regeneration in a bovine model of disc injury.
Method: Seven sheep received one of the following interventions at four lumbar discs: 1) annular puncture plus 300 µg BMP-13 injection in 70 µg saline; 2) annular puncture plus 70 µg saline injection alone; 3) surgical exposure only (exposed control); or 4) no surgical exposure (nonvisualized control).
Radiographs were taken immediately postsurgery, at day 14 postsurgery, and following euthanasia (4, 8 or 12-month postsurgery). The disc height index (DHI) was obtained and compared. MRI and CT scans were obtained when the spine was harvested. Histologic analysis also was performed at each euthanasia.
Results: Annual perforation caused signs of disc deterioration as early as 4 months after injury, as demonstrated by loss of extracellular matrix proteins, disc narrowing, and water loss. The sheep that received BMP-13 showed improvements in the following parameters: cell numbers in the nucleus pulposus and annulus fibrosus, disc narrowing, collagen production, and proteoglycan production.
Conclusion: BMP-13, when injected at the time of injury, reversed or stopped the histological changes found in controls, including loss of extracellular matrix proteins. In addition, BMP-13 was linked to greater hydration at 4 months and more cells in the nucleus pulposus.
The paper examines the effects of BMP-13 on disc regeneration in a sheep animal model of disc annular injury. BMP-13, unlike other BMPs, appears to promote chondrocyte marker gene expression in a variety of cells, while at the same time seems to inhibit early and late markers of osteogenic differentiation in vitro.
An annular injury was performed on four lumbar discs in each of 7 male merino wethers. One of the punctured levels received 300 µg of BMP-13 in 70 (1 saline, while another disc received just saline alone.
The discs injected with BMP-13 had normal DHI and upregulated levels of cellular functions that are necessary for disc regeneration, including increased neo-vascularization, chondrocyte production, collagen production, and proteoglycan production when compared to the stabbed disc and levels close to or equal to the control disc. Thus, this study suggests that BMP-13 may be able to slow disc degeneration.
Attempts at treating disc degeneration, which occurs not only in the nucleus pulposus but also within the annulus fibrosus, is usually directed at treating only the nucleus pulposus component. This paper is important since it addresses a possible approach to treating the annular defects that often accompany disc degeneration. Most other papers have discussed and examined a cellular approach.