The Role of Bone Morphogenetic Proteins 2, 7, and 14 in Approaches for Intervertebral Disk Restoration

Bone morphogenetic proteins (BMPs) are a group of cytokines in the transforming growth factor beta superfamily. Transforming growth factor beta originally was described as a group of substances that have the ability to produce exostosis formation, but it was later discovered to have a wide range of chondroinductive and osteoinductive actions during embryogenesis and later in life. Recombinant BMPs were successfully introduced into clinical practice for augmentation of bone fusion in spinal and orthopedic surgeries; however, BMPs are now gaining attention from researchers for their role in intervertebral disk (IVD) pathology. We summarize the current understanding and future directions for the role of BMPs in IVD degradation and restoration. Recombinant human BMP-2, a component of INFUSE bone graft (Medtronic, Minneapolis, Minnesota, USA), was the first clinically available BMP drug. INFUSE bone grafts are used to enhance bone formation in lumbar fusion procedures, decreasing the rate of nonunions compared with autologous iliac crest bone grafts. It is also approved by the U.S. Food and Drug Administration for several other bone fusion procedures. Initial studies for BMP-2 in the IVD showed regenerative potential in the nucleus pulposus, where BMP2 resulted in a mitogenic effect and stimulated proteoglycan synthesis without ossification; additionally, studies in explanted rabbit IVDs showed that the presence of BMP-2 favorably increased expression of collagen II and aggrecans, while decreasing expression of catabolic matrix metalloproteinases in the anulus fibrosus. However, BMP-2 also decreased glycosaminoglycan content and increased type I collagen production in the nucleus pulposus as well as initiating ossification of the anulus fibrosus. Furthermore, exogenous application of BMP-2 can accelerate osteophyte formation, typically seen clinically in late-stage degenerative disk disease as a compensatory mechanism for spinal instability. Endogenous BMP-2 in the IVD increases with age and in mechanically induced models of disk degeneration. Recombinant human BMP-7, also known as osteogenic protein1, is currently marketed as OP-1 (Stryker Biotech, Hopkinton, Massachusetts, USA), an aid for posterior spinal fusion and long