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Ossification of the posterior longitudinal ligament (OPLL) in the spine is caused by systemic and/or regional factors affecting the regulation of osteocartilaginous formation and maintenance. The aims of this study were to elucidate the relationship between the degeneration of the intervertebral discs and changes in the posterior longitudinal ligament (PLL) in the tiptoe walking (ttw) mouse, an animal model of OPLL, and to analyze the sequential changes of the cells producing extracellular matrix components using immunohistochemical methods. At 6 weeks of age, the discs degenerated and the chondrocytes in the nucleus pulposus were positive for chondroitin-6-sulfate in the ttw mice. The fibroblasts in the PLL at the disc level were positively stained with type II and XI collagens. At 14 weeks, the discs herniated into the thickened PLL, and chondrocyte-like cells appeared in the PLL at vertebral endplate level. At 18 and 22 weeks, the number of chondrocyte-like cells increased in the PLL and expressed type I collagen. A potent regional factor causing OPLL in the ttw mice appears to be the initial degeneration and subsequent herniation of the nucleus pulposus. These sequential changes in the ttw mice were accelerated by administration of etidronate. It was suggested that etidronate stimulated the cartilaginous hyperplasia in the PLL of the ttw mice. It appeared as if the PLL transformed itself into cartilaginous tissue to repair the degeneration of the intervertebral disc.