Safranin-O-stained sections reflecting typical histologic changes after injection of control small interfering RNA (siRNA) or ADAMTS5 siRNA in the rabbit anular puncture model of disc degeneration. Eight weeks after the control or ADAMTS5 siRNA injections, the control siRNA group displayed a complete loss of nucleus pulposus (NP) tissues, which had been replaced by a fibrocartilaginous tissue (a, c). The severely degenerated discs that had received the control siRNA showed a loss of proteoglycans and the collapsed, wavy fibrocartilage lamellae typical of the anulus fibrosus (AF), with associated fibrochondrocytes (e, g). In the ADAMTS5 siRNA-injected discs, safranin-O staining demonstrated the maintenance of intervertebral disc structure with a lightly stained matrix and large cells (b, d); the NP was rounded and bloated looking, and consisted of numerous large, vacuolated cells and smaller chondrocyte-like cells (f, h). A clear demarcation was seen between the NP and inner anulus in the ADAMTS5 siRNA-injected discs. (Magnification ×20 (a-d), ×100 (e-h)). The level in a, b, e, and f is L2/3, and in c, d, g, and h is L4/5.