A Mouse Intervertebral Disc Degeneration Model by Surgically Induced Instability.

Abstract

An experimental study to develop a mouse model of lumbar intervertebral disc degeneration (IDD). The aim of this study was to develop a mouse lumbar IDD model using surgically induced instability and to compare the findings of this model to those in human IDD. Previously, various kinds of inducers have been used to reproduce IDD in experimental animals; however, there is yet no standard mouse lumbar IDD model without direct injury to intervertebral disc. A total number of 59 C57BL/6J male mice at 8 weeks old were used. Instability of lumbar spine was induced by surgical resection of posterior elements, including facet joints, supra- and interspinous ligaments. We then analyzed time course changes in radiographical (n = 17) and histological analyses (n = 42), and compared these findings with those in human IDD. Radiographical analyses showed that the disc height began to decrease in the first 2 weeks after the surgery, and the decrease continued throughout 12 weeks. Bone spurs at the vertebral rims were observed in the late stage of 8 and 12 weeks after the surgery. Histological analyses showed that the disorder of the anterior anulus fibrosus (AF) was initially obvious, followed by posterior shift and degeneration of the nucleus pulposus (NP). Proteoglycan detected in inner layer of AF and periphery of NP was decreased after 8 weeks. Immunohistochemistry displayed the increase of type I and X collagen, and matrix metalloproteinase 13 in the anterior AF. Surgical resection of posterior elements of mouse lumbar spine resulted in reproducible IDD. Because the present procedure does not employ direct injury to intervertebral disc and the radiological and histological findings are compatible with those in human IDD, it may contribute to further understanding of the native pathophysiology of IDD in future. N/A.