A mouse coccygeal intervertebral disc degeneration model with tail-looping constructed using a suturing method

Abstract

Backgroud: Intervertebral disc degeneration (IDD) is one of the common degenerative diseases. Due to ethical constraints, it is difficult to obtain sufficient research on humans, so the use of an animal model of IDD is very important to clarify the pathogenesis and treatment mechanism of the disease.

Methods: In this study, thirty 2-month-old mice were selected for operation to establish a coccygeal IDD model. The distal tail portion of the tail (beyond the 17th coccygeal vertebra) and a small piece of skin above the 8th coccygeal vertebra were excised, and the two incisions were brought together after flexion, and secured with sutures. The heights and signal intensities of the intervertebral discs (IVDs) were assessed using microcomputed tomography (μCT) and magnetic resonance imaging (MRI) at 0, 6, 12 weeks postoperatively. The overall tissue morphology, cell distribution and density, and extracellular matrix of the IVDs were also assessed using Hematoxylin and Eosin (HE), Safranin O-Fast Green and immunohistochemical staining.

Results: All mice in the experimental group survived after the operation, and there were no complications such as wound infection, tail necrosis and suture shedding. The experimental results demonstrated that the suturing method can successfully initiate IDD. Different severity levels of IDD can be induced by controlling the bending angle of the IVDs within the tail loop; however, for consistency, histologic and imaging results should be obtained at the same bending angle and looping period.

Conclusions: This IDD model is an effective method for studying the etiology and treatment of degenerative IVD disease.

Keywords

animal model / intervertebral disc degeneration / mechanical stress / mice

References

[1] Francisco V, Pino J, González-Gay MÁ, et al. A new immunometabolic perspective of intervertebral disc degeneration. Nat Rev Rheumatol. 2022; 18(1): 47-60.

[2] Costăchescu B, Niculescu AG, Teleanu RI, et al. Recent advances in managing spinal intervertebral discs degeneration. Int J Mol Sci. 2022; 23(12): 6460.

[3] Hasvik E, Haugen AJ, Grøvle L. Pinprick and light touch are adequate to establish sensory dysfunction in patients with lumbar radicular pain and disc herniation. Clin Orthop Relat Res. 2021; 479(4): 651-663.

[4] Cyril D, Giugni A, Bangar SS, et al. Elastic fibers in the intervertebral disc: from form to function and toward regeneration. Int J Mol Sci. 2022; 23(16): 8931.

[5] Lee S, Millecamps M, Foster DZ, Stone LS. Long-term histological analysis of innervation and macrophage infiltration in a mouse model of intervertebral disc injury-induced low back pain. J Orthop Res. 2020; 38(6): 1238-1247.

[6] Xi Y, Kong J, Liu Y, et al. Minimally invasive induction of an early lumbar disc degeneration model in rhesus monkeys. Spine (Phila Pa 1976). 2013; 38(10): E579-E586.

[7] Zhang C, Gullbrand SE, Schaer TP, et al. Inflammatory cytokine and catabolic enzyme expression in a goat model of intervertebral disc degeneration. J Orthop Res. 2020; 38(11): 2521-2531.

[8] Choi H, Tessier S, Silagi ES, et al. A novel mouse model of intervertebral disc degeneration shows altered cell fate and matrix homeostasis. Matrix Biol. 2018; 70: 102-122.

[9] Glaser S, Anastassiadis K, Stewart AF. Current issues in mouse genome engineering. Nat Genet. 2005; 37(11): 1187-1193.

[10] Ashinsky BG, Bonnevie ED, Mandalapu SA, et al. Intervertebral disc degeneration is associated with aberrant endplate remodeling and reduced small molecule transport. J Bone Miner Res. 2020; 35(8): 1572-1581.

[11] Cheng Z, Xiang Q, Wang J, Zhang Y. The potential role of melatonin in retarding intervertebral disc ageing and degeneration: a systematic review. Ageing Res Rev. 2021; 70: 101394.

[12] He S, Zhang Y, Zhou Z, et al. Similarity and difference between aging and puncture-induced intervertebral disc degeneration. J Orthop Res. 2022; 40(11): 2565-2575.

[13] Lin D, Alberton P, Delgado Caceres M, et al. Loss of tenomodulin expression is a risk factor for age-related intervertebral disc degeneration. Aging Cell. 2020; 19(3): e13091.

[14] Yang S, Zhang F, Ma J, Ding W. Intervertebral disc ageing and degeneration: the antiapoptotic effect of oestrogen. Ageing Res Rev. 2020; 57: 100978.

[15] Ji Y, Zhu P, Zhang L, Yang H. A novel rat tail disc degeneration model induced by static bending and compression. Animal Model Exp Med. 2021; 4(3): 261-267.

[16] Patterson F, Miralami R, Tansey KE, Prabhu RK, Priddy LB. Deleterious effects of whole-body vibration on the spine: a review of in vivo, ex vivo, and in vitro models. Animal Model Exp Med. 2021; 4(2): 77-86.

[17] Desmoulin GT, Pradhan V, Milner TE. Mechanical aspects of intervertebral disc injury and implications on biomechanics. Spine (Phila Pa 1976). 2020; 45(8): E457-E464.

[18] Culbert MP, Warren JP, Dixon AR, Fermor HL, Beales PA, Wilcox RK. Evaluation of injectable nucleus augmentation materials for the treatment of intervertebral disc degeneration. Biomater Sci. 2022; 10(4): 874-891.

[19] Sakai D, Nishimura K, Tanaka M, et al. Migration of bone marrow-derived cells for endogenous repair in a new tail-looping disc degeneration model in the mouse: a pilot study. Spine J. 2015; 15(6): 1356-1365.

[20] Tamagawa S, Sakai D, Nojiri H, et al. SOD2 orchestrates redox homeostasis in intervertebral discs: a novel insight into oxidative stress-mediated degeneration and therapeutic potential. Redox Biol. 2024; 71: 103091.

[21] Melgoza IP, Chenna SS, Tessier S, et al. Development of a standardized histopathology scoring system using machine learning algorithms for intervertebral disc degeneration in the mouse model-an ORS spine section initiative. JOR Spine. 2021; 4(2): e1164.

[22] Yang B, Wendland MF, O'Connell GD. Direct quantification of intervertebral disc water content using MRI. J Magn Reson Imaging. 2020; 52(4): 1152-1162.

[23] Gorth DJ, Shapiro IM, Risbud MV. A new understanding of the role of IL-1 in age-related intervertebral disc degeneration in a murine model. J Bone Miner Res. 2019; 34(8): 1531-1542.

[24] Yurube T, Hirata H, Ito M, et al. Involvement of autophagy in rat tail static compression-induced intervertebral disc degeneration and notochordal cell disappearance. Int J Mol Sci. 2021; 22(11): 5648.

[25] Chang HI, Chen CN, Huang KY. Mechanical stretch-induced NLRP3 inflammasome expression on human annulus fibrosus cells modulated by endoplasmic reticulum stress. Int J Mol Sci. 2022; 23(14): 7951.

[26] Che YJ, Guo JB, Liang T, et al. Controlled immobilization-traction based on intervertebral stability is conducive to the regeneration or repair of the degenerative disc: an in vivo study on the rat coccygeal model. Spine J. 2019; 19(5): 920-930.

[27] Lai A, Chow DH, Siu SW, et al. Effects of static compression with different loading magnitudes and durations on the intervertebral disc: an in vivo rat-tail study. Spine (Phila Pa 1976). 2008; 33(25): 2721-2727.

[28] Millecamps M, Lee S, Foster DZ, Stone LS. Disc degeneration spreads: long-term behavioural, histologic and radiologic consequences of a single-level disc injury in active and sedentary mice. Eur Spine J. 2021; 30(8): 2238-2246.

[29] Liu Q, Wang X, Hua Y, et al. Estrogen deficiency exacerbates intervertebral disc degeneration induced by spinal instability in rats. Spine (Phila Pa 1976). 2019; 44(9): E510-E519.

[30] Lindblom K. Experimental ruptures of intervertebral discs in rats' tails; a preliminary report. J Bone Joint Surg Am. 1952; 34-A(1): 123-128.

[31] Lindblom K. Intervertebral-disc degeneration considered as a pressure atrophy. J Bone Joint Surg Am. 1957; 39-A(4): 933-945.

[32] Berg-Johansen B, Fields AJ, Liebenberg EC, Li A, Lotz JC. Structure-function relationships at the human spinal disc-vertebra interface. J Orthop Res. 2018; 36(1): 192-201.

[33] Ranganathan K, Loder S, Agarwal S, et al. Heterotopic ossification: basic-science principles and clinical correlates. J Bone Joint Surg Am. 2015; 97(13): 1101-1111.

[34] Shi L, Miao J, Chen D, Shi J, Chen Y. Endoplasmic reticulum stress regulates mechanical stress-induced ossification of posterior longitudinal ligament. Eur Spine J. 2019; 28(10): 2249-2256.

[35] Zhao Y, Yuan B, Cheng L, et al. Cyclic tensile stress to rat thoracolumbar ligamentum flavum inducing the ossification of ligamentum flavum: an in vivo experimental study. Spine (Phila Pa 1976). 2021; 46(17): 1129-1138.

[36] Pauli D, von Treuheim T, Torre OM, Ferreri ED, et al. Tenomodulin and chondromodulin-1 are both required to maintain biomechanical function and prevent intervertebral disc degeneration. Cartilage. 2021; 13(2_suppl): 604S-614S.

[37] Zhang D, Jin L, Reames DL, Shen FH, Shimer AL, Li X. Intervertebral disc degeneration and ectopic bone formation in apolipoprotein E knockout mice. J Orthop Res. 2013; 31(2): 210-217.

[38] Wade K, Berger-Roscher N, Rasche V, Wilke H. Disc wall structural abnormalities can act as initiation sites for herniation. Eur Cell Mater. 2020; 40: 227-238.

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2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.