Osteogenic Protein-1 **(OP-1) Injection into a Degenerated Disc Induced the Recovery of Disc Height, MRI and Histochemical Changes in the Rabbit Annular Puncture Model

Summary: This is the first study to investigate the effect of OP-1 (BMP-7) on the in vivo rabbit intervertebral disc degeneration model. A single injection of OP-1 restored the disc height, improved the MRI and histologic grades, and increased the proteogylcan and collagen contents. This study gives evidence that biological repair or regeneration is feasible by injecting growth factors into the degenerated disc.

Introduction: Growth factors, such as osteogenic protein-1** (OP-1 or BMP-7) have the ability to stimulate synthesis of proteoglycan and collagen in vitro. This study investigates the in vivo effects of OP-1 injection in the rabbit model by a needle puncture.

Methods: 60 New Zealand white rabbits received an annulus puncture in two non-contiguous discs with an 18G needle to induce disc degeneration. Four weeks later, 5% lactose (10 _l) or OP-1 (100 _g in 10 _l ) were injected into NP. The disc height was followed radiographically up to 24 weeks after injection. At 2-, 4-, 8-. 12, and 24-weeks after the injection, rabbits were sacrificed for MRI and histology as well as the proteoglycan content.

Results: The annulus puncture induced a consistent disc narrowing within 4 weeks. The injection of OP-1 induced a restoration of disc height at 6 weeks that was sustained to 24 weeks, while no change was noted with lactose injection. The MRI grading showed a significant difference at the 8-, 12, and 12- week time points. Histologically, OP-1 groups showed greater chodrocytic cells with matrix and higher histologic grades and the proteoglycan content was higher.

Discussion: This study is the first report on the effect of growth factor such as OP-1, demonstrating the feasibility of restoring degenerative discs by a single injection of OP-1 in the rabbit. Importantly, the effect of OP-1 injection was sustained up to 24 weeks. Biological repair or regeneration of the degenerated discs is feasible by growth factor injection and further preclinical studies and clinical trial are needed to determine if pain and outcomes will be altered by restoring the matrices in the discs.

FDA Diclosure Cleared: No **OP-1 for intervertebral disc repair