2021 Volume No 42 – pages 90-109
Title: NF-kB decoy oligodeoxynucleotide preserves disc height in a rabbit anular-puncture model and reduces pain induction in a rat xenograft-radiculopathy model |
Authors: K Kato, K Akeda, S Miyazaki, J Yamada, C Muehleman, K Miyamoto, YA Asanuma, K Asanuma, T Fujiwara, ME Lenz, T Nakazawa, H An, K Masuda |
Address: Department of Orthopedic Surgery, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA |
E-mail: komasuda at ucsd.edu |
Abstract: While it is known that the degenerated intervertebral disc (IVD) is one of the primary reasons for low-back pain and subsequent need for medical care, there are currently no established effective methods for direct treatment. Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes’ expression, among which are inflammatory cytokines, in many tissues including the IVD. NF-κB decoy is an oligodeoxynucleotide containing the NF-κB binding site that entraps NF-κB subunits, resulting in suppression of NF-κB activity. In the present preclinical study, NF-κB decoy was injected into degenerated IVDs using the rabbit anular-puncture model. In terms of distribution, NF-κB decoy persisted in the IVDs up to at least 4 weeks after injection. The remaining amount of NF-κB decoy indicated that it fit a double-exponential-decay equation. Investigation of puncture-caused degeneration of IVDs showed that NF-κB decoy injection recovered, dose-dependently, the reduced disc height that was associated with reparative cell cloning and morphological changes, as assessed through histology. Gene expression, by quantitative real-time polymerase chain reaction (qRT-PCR), showed that NF-κB decoy attenuated inflammatory gene expression, such as that of interleukin-1 and tumor necrosis factor-α, in rabbit degenerated IVDs. NF-κB decoy also reduced the pain response as seen using the “pain sensor” nude rat xenograft-radiculopathy model. This is the first report demonstrating that NF-κB decoy suppresses the inflammatory response in degenerated IVDs and restores IVD disc height loss. Therefore, the intradiscal injection of NF-κB decoy may have the potential as an effective therapeutic strategy for discogenic pain associated with degenerated IVDs. |
Key Words: Intervertebral disc-repair/regeneration, intervertebral disc-degeneration, animal models-general, nuclear factor-κB, decoy, intervertebral disc-histology, intradiscal injection, translational and preclinical research. |
Publication date: July 20th 2021 |
Article download: Pages 90-109 (PDF file) |
