Development of a Unique Mouse Intervertebral Disc Degeneration Model Using a Simple Novel Tool

다국어 초록 (Multilingual Abstract)

Study Design: Animal case control study.Purpose: To create a simple, reproducible disc degeneration model for mouse coccygeal vertebrae. Overview of Literature: Back pain due to disc degeneration is probably the most common problem encountered in neurosurgical practice. An easily reproducible animal model for disc degeneration will help in understanding its pathophysiology, and serve as a platform for examining various therapeutic options.Methods: A total of 18 mice were divided into injured (n=12) and non-injured (n=6) groups. The disc height index (DHI%) at coccygeal 4–5 level was measured by computed tomography (CT) scan for all mice. Coccygeal 4–5 discs of the injury group were injured using a 32G needle fixed to a novel tool and confirmed by CT. The non-injury group underwent no procedure. DHI% was measured by CT at 2-, 4-, and 6-week post-injury, and all mice tails were sectioned for histopathology grading of disc degeneration at the respective time intervals.Results: The injured group showed significant variation in DHI% at 2, 4, and 6 weeks, whereas there was no change in the noninjured group. Histopathologic evaluation with Safranin O stain showed a worsening of the disc degeneration score at 2, 4, and 6 weeks in the injured group, but in the non-injured group there was no change. Percutaneous needle injury technique with our novel tool provided 100% accuracy and uniform degeneration.Conclusions: A simple, easily reproducible mouse model for disc degeneration was created using a simple, cost-effective, novel tool and technique, its advantage being high precision and user friendly.

참고문헌 (Reference)

1 Zhang H, "Time course investigation of intervertebral disc degeneration produced by needle-stab injury of the rat caudal spine : laboratory investigation" 15 : 404-413, 2011

2 Chen CH, "Time course investigation of intervertebral disc degeneration in a rat-tail puncture model" 156 : 15-20, 2016

3 Smit TH, "The use of a quadruped as an in vivo model for the study of the spine : biomechanical considerations" 11 : 137-144, 2002

4 Elliott DM, "The effect of relative needle diameter in puncture and sham injection ani-mal models of degeneration" 33 : 588-596, 2008

5 Ching CT, "The effect of cyclic compression on the mechanical properties of the inter-vertebral disc : an in vivo study in a rat tail model" 18 : 182-189, 2003

6 Kiester DP, "The dose-related effect of intradiscal chymopapain on rabbit intervertebral discs" 19 : 747-751, 1994

7 Rousseau MA, "Stab incision for inducing intervertebral disc degeneration in the rat" 32 : 17-24, 2007

8 Hoogendoorn RJ, "Reproducible long-term disc degeneration in a large animal model" 33 : 949-954, 2008

9 Piazza M, "Quantitative MRI correlates with histological grade in a percutaneous needle injury mouse model of disc degeneration" 36 : 2771-2779, 2018

10 Sahlman J, "Premature vertebral endplate ossification and mild disc degeneration in mice after inactivation of one allele belonging to the Col2a1 gene for type II collagen" 26 : 2558-2565, 2001

11 Kroeber MW, "New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration" 27 : 2684-2690, 2002

12 Yang F, "Mesenchymal stem cells arrest intervertebral disc degeneration through chondrocytic differentiation and stimulation of endogenous cells" 17 : 1959-1966, 2009

13 Taher F, "Lumbar degenerative disc disease : current and future concepts of diagnosis and management" 2012 : 970752-, 2012

14 Ullah I, "Human mesenchymal stem cells : current trends and future prospective" 35 : e00191-, 2015

15 Issy AC, "Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats" 46 : 235-244, 2013

16 Kim KS, "Disc degeneration in the rabbit : a biochemical and radiological comparison between four disc injury models" 30 : 33-37, 2005

17 Sakai D, "Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model : potential and limitations for stem cell therapy in disc regeneration" 30 : 2379-2387, 2005

18 Urban JP, "Degeneration of the intervertebral disc" 5 : 120-130, 2003

19 O’Connell GD, "Comparison of animals used in disc research to human lumbar disc geometry" 32 : 328-333, 2007

20 Squillaro T, "Clinical trials with mesenchymal stem cells : an update" 25 : 829-848, 2016

21 Alini M, "Are animal models useful for studying human disc disorders/degeneration?" 17 : 2-19, 2008

22 Lotz JC, "Animal models of intervertebral disc degeneration : lessons learned" 29 : 2742-2750, 2004

23 Jin L, "Animal models for disc degeneration : an update" 33 : 543-554, 2018

24 Norcross JP, "An in vivo model of degenerative disc disease" 21 : 183-188, 2003

25 Han B, "A simple disc degeneration model induced by percutaneous needle puncture in the rat tail" 33 : 1925-1934, 2008

26 Daly C, "A review of animal models of intervertebral disc degeneration : pathophysiology, regeneration, and translation to the clinic" 2016 : 5952165-, 2016

27 Masuda K, "A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture : correlation between the degree of disc injury and radiological and histological appearances of disc degeneration" 30 : 5-14, 2005

28 Choi H, "A novel mouse model of intervertebral disc degeneration shows altered cell fate and matrix homeostasis" 70 : 102-122, 2018