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The etiology of degenerative disc disease is unknown. Several investigators have reported the presence of proteolytic enzymes, such as the matrix metalloproteinase (MMP) and ADAMTS (a disintegrin and metalloprotease with thrombospondin-like repeats) families, in degenerated human discs. Glasson and colleagues recently reported that a significant reduction occurs in the severity of cartilage destruction in  ADAMTS5  knockout mice compared with wild-type mice. The purpose of this study was to evaluate the suppressive effects of injections of  ADAMTS5  small interference RNA (siRNA) oligonucleotide on intervertebral disc degeneration in the rabbit anular needle-puncture model.    Methods  Rabbit nucleus pulposus (NP) cells were transfected with siRNA oligonucleotides specific for  ADAMTS5  or the control. The suppression of the  ADAMTS5  gene by siRNA transfection was assessed by using real-time polymerase chain reaction (PCR), both in monolayer and alginate bead cultures with or without interleukin-1β (IL-1β) stimulation. The effect of siRNA was determined  in vivo  by using the rabbit anular needle-puncture model (control group: n = 8; ADAMTS5 group: n = 8). One week after the initial anular puncture, the animals received an injection of the control or anti- ADAMTS5  oligonucleotide (100 μg each at the L2/3 and L4/5 level; 16 discs/group). Disc height, magnetic resonance imaging (MRI) (Thompson classification and signal intensity), and safranin-O staining (histologic grade) were assessed.    Results  IL-1β treatment significantly increased the  ADAMTS5  mRNA level in NP cells ( P  &lt; 0.01).  ADAMTS5  gene suppression was 70% compared with the control oligonucleotide in both monolayer and alginate bead culture with or without stimulation with IL-1β. The injection of anti- ADAMTS5  oligonucleotide  in vivo  resulted in improved MRI scores with increased signal intensity and improved histologic grade scores with statistical significance ( P  &lt; 0.05). No significant change in disc height was observed.    Conclusions  A single injection of  ADAMTS5  siRNA induced the suppression of degradation in NP tissues, as shown by significantly improved MRI and histologic grades. The mechanism of response to siRNA may be worthy of exploration for possible therapeutic purposes.

Effect of small interference RNA (siRNA) for ADAMTS5on intervertebral disc degeneration in the rabbit anular needle-puncture model