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An in vivo study of the cervical intervertebral discs (IVDs) response to upright posture was performed using an amputated bipedal rat model.To investigate the effects of upright posture on IVDs of rat cervical spine.The distinct arrangement of human neck muscle from that of cat and rhesus indicated that in the evolution process, upright posture might have affected cervical spine of human ancestors. However, the effects of upright posture on cervical spine have not been assessed.Forty-one-month-old rats were randomly divided into 5-month-control, 5-month-surgery, 7-month-control, and 7-month surgery group (n = 10 per group). Both forelimbs of 2 surgery group rats were amputated, and those rats were then induced to be upright in the custom-made cages. Two control group rats were kept in regular cages. These rats were respectively killed at the fifth and seventh month after surgery and the IVD samples of lumbar spine were harvested for histologic and immunohistochemical studies. Total RNA isolated from these samples were used for real-time polymerase chain reaction of type II collagen (Col2a1), type X collagen, matrix metalloproteinase 13 (MMP-13), MMP-3, aggre-can, and aggrecanase-2 (ADAMTS-5).Upright posture affects histologic changes of the cervical IVDs such as fissures of anulus fibrosus and decreased height of disc, decreased protein level of Col2a1 at nucleus pulposus and anulus fibrosus, up-regulated MMP-13, MMP-3, ADAMTS-5, and type X collagen mRNA expression, and downregulated mRNA expression of Col2a1 and aggrecan.Upright stance accelerates cervical disc degeneration in rats.