Background: Research has demonstrated that excessive loading can induce intervertebral disc degeneration (IDD). However, existing animal models have inherent limitations, and there is still no reliable model to investigate the effects of excessive loading on IDD. This study aims to develop an in vitro model of simulated excessive loading.
Methods: A total of 24 twelve-week-old Sprague–Dawley rats with similar body weights were randomly divided into four groups. In the compression suture group, a 5-mm-wide tail skin was removed, and the defect was compressed sutured with 2–0 silk thread. In the sham surgery group, only a 5-mm-wide tail skin was removed without compression suturing. All animals underwent radiological, histological, and molecular analysis at 2, 6, and 10 weeks postoperatively.
Results: X-rays and magnetic resonance imaging showed that the height of the intervertebral disc (IVD) and the water content of the nucleus pulposus (NP) decreased in the compression suture group. The histological results showed that the tissue structure of IVDs was disordered, and the proteoglycan content was reduced in the compression group. Compression induced upregulation of MMP-3 and MMP-13 expression in NP cells, whereas the expression of collagen II and aggrecan was downregulated. Additionally, an increased inflammatory response and apoptosis level were detected in NP cells of the compression group.
Conclusion: We conclude that simulated excessive loading induces IDD in rats. This is a reliable and highly reproducible IDD model that will provide a foundation to investigate the effects of excessive loading on IDD.
| [1] |
Zheng CJ, Chen J. Disc degeneration implies low back pain. Theor Biol Med Model. 2015; 12:24.
|
| [2] |
Weber KT, Jacobsen TD, Maidhof R, et al. Developments in intervertebral disc disease research: pathophysiology, mechanobiology, and therapeutics. Curr Rev Musculoskelet Med. 2015; 8(1): 18-31.
|
| [3] |
Cheung KM, Karppinen J, Chan D, et al. Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-three individuals. Spine. 2009; 34(9): 934-940.
|
| [4] |
Bian Q, Ma L, Jain A, et al. Mechanosignaling activation of TGFβ maintains intervertebral disc homeostasis. Bone Res. 2017; 5:17008.
|
| [5] |
Vo N, Seo HY, Robinson A, et al. Accelerated aging of intervertebral discs in a mouse model of progeria. J Orthop Res. 2010; 28(12): 1600-1607.
|
| [6] |
Adams MA, Hutton WC. The effect of posture on the role of the apophysial joints in resisting intervertebral compressive forces. J Bone Joint Surg Br. 1980; 62(3): 358-362.
|
| [7] |
Noonan AM, Brown SHM. Paraspinal muscle pathophysiology associated with low back pain and spine degenerative disorders. JOR Spine. 2021; 4(3):e1171.
|
| [8] |
Sebro R, O'Brien L, Torriani M, Bredella MA. Assessment of trunk muscle density using CT and its association with degenerative disc and facet joint disease of the lumbar spine. Skeletal Radiol. 2016; 45(9): 1221-1226.
|
| [9] |
Liang H, Ma SY, Feng G, Shen FH, Joshua Li X. Therapeutic effects of adenovirus-mediated growth and differentiation factor-5 in a mice disc degeneration model induced by annulus needle puncture. Spine J. 2010; 10(1): 32-41.
|
| [10] |
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.
|
| [11] |
Huang Y, Zhang Z, Wang J, et al. circSPG21 protects against intervertebral disc disease by targeting miR-1197/ATP1B3. Exp Mol Med. 2021; 53(10): 1547-1558.
|
| [12] |
Xie W, Huang Z, Huang Z, et al. A mouse coccygeal intervertebral disc degeneration model with tail-looping constructed using a suturing method. Animal Model Exp Med. 2025; 8: 1645-1655.
|
| [13] |
Lotz JC, Colliou OK, Chin JR, Duncan NA, Liebenberg E. Compression-induced degeneration of the intervertebral disc: an in vivo mouse model and finite-element study. Spine (Phila Pa 1976). 1998; 23(23): 2493-2506.
|
| [14] |
Yurube T, Nishida K, Suzuki T, et al. Matrix metalloproteinase (MMP)-3 gene up-regulation in a rat tail compression loading-induced disc degeneration model. J Orthop Res. 2010; 28(8): 1026-1032.
|
| [15] |
Cassidy JD, Yong-Hing K, Kirkaldy-Willis WH, Wilkinson AA. A study of the effects of bipedism and upright posture on the lumbosacral spine and paravertebral muscles of the Wistar rat. Spine (Phila Pa 1976). 1988; 13(3): 301-308.
|
| [16] |
Liang QQ, Cui XJ, Xi ZJ, et al. Prolonged upright posture induces degenerative changes in intervertebral discs of rat cervical spine. Spine (Phila Pa 1976). 2011; 36(1): E14-E19.
|
| [17] |
Liu Z, Zhou Q, Zheng J, Li C, Zhang W, Zhang X. A novel in vivo mouse intervertebral disc degeneration model induced by compressive suture. Exp Cell Res. 2021; 398(1):112359.
|
| [18] |
Tang SN, Walter BA, Heimann MK, et al. In vivo mouse intervertebral disc degeneration models and their utility as translational models of clinical Discogenic Back pain: a comparative review. Front Pain Res (Lausanne). 2022; 3:894651.
|
| [19] |
Kudelko M, Chen P, Tam V, et al. PRIMUS: comprehensive proteomics of mouse intervertebral discs that inform novel biology and relevance to human disease modelling. Matrix Biol Plus. 2021; 12:100082.
|
| [20] |
Tam V, Chan WCW, Leung VYL, et al. Histological and reference system for the analysis of mouse intervertebral disc. J Orthop Res. 2018; 36(1): 233-243.
|
| [21] |
Boyd LM, Richardson WJ, Chen J, Kraus VB, Tewari A, Setton LA. Osmolarity regulates gene expression in intervertebral disc cells determined by gene array and real-time quantitative RT-PCR. Ann Biomed Eng. 2005; 33(8): 1071-1077.
|
| [22] |
Urban JP. The role of the physicochemical environment in determining disc cell behaviour. Biochem Soc Trans. 2002; 30(Pt 6): 858-864.
|
| [23] |
Fukui D, Kawakami M, Yoshida M, Nakao S, Matsuoka T, Yamada H. Gait abnormality due to spinal instability after lumbar facetectomy in the rat. Eur Spine J. 2015; 24(9): 2085-2094.
|
| [24] |
Xia W, Zhang LL, Mo J, et al. Effect of static compression loads on intervertebral disc: an in vivo bent rat tail model. Orthop Surg. 2018; 10(2): 134-143.
|
| [25] |
Court C, Colliou OK, Chin JR, Liebenberg E, Bradford DS, Lotz JC. The effect of static in vivo bending on the murine intervertebral disc. Spine J. 2001; 1(4): 239-245.
|
| [26] |
Hirata H, Yurube T, Kakutani K, et al. A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype. J Orthop Res. 2014; 32(3): 455-463.
|
| [27] |
Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine (Phila Pa 1976). 2006; 31(18): 2151-2161.
|
| [28] |
Mohanty S, Pinelli R, Pricop P, Albert TJ, Dahia CL. Chondrocyte-like nested cells in the aged intervertebral disc are late-stage nucleus pulposus cells. Aging Cell. 2019; 18(5):e13006.
|
| [29] |
Mizrahi O, Sheyn D, Tawackoli W, et al. Nucleus pulposus degeneration alters properties of resident progenitor cells. Spine J. 2013; 13(7): 803-814.
|
| [30] |
Sivan SS, Hayes AJ, Wachtel E, et al. Biochemical composition and turnover of the extracellular matrix of the normal and degenerate intervertebral disc. Eur Spine J. 2014; 23(Suppl 3): S344-S353.
|
| [31] |
Walsh AJ, Lotz JC. Biological response of the intervertebral disc to dynamic loading. J Biomech. 2004; 37(3): 329-337.
|
| [32] |
Urban JP, Roberts S. Degeneration of the intervertebral disc. Arthritis Res Ther. 2003; 5(3): 120-130.
|
| [33] |
Larson JW, Levicoff EA, Gilbertson LG, et al. Biologic modification of animal models of intervertebral disc degeneration. J Bone Joint Surg Am. 2006; 88(Suppl 2): 83-87.
|
| [34] |
Fu F, Bao R, Yao S, et al. Aberrant spinal mechanical loading stress triggers intervertebral disc degeneration by inducing pyroptosis and nerve ingrowth. Sci Rep. 2021; 11(1): 772.
|
| [35] |
Shi S, Kang XJ, Zhou Z, He ZM, Zheng S, He SS. Excessive mechanical stress-induced intervertebral disc degeneration is related to Piezo1 overexpression triggering the imbalance of autophagy/apoptosis in human nucleus pulpous. Arthritis Res Ther. 2022; 24(1): 119.
|
| [36] |
Gao G, He J, Nong L, et al. Periodic mechanical stress induces the extracellular matrix expression and migration of rat nucleus pulposus cells by upregulating the expression of intergrin α1 and phosphorylation of downstream phospholipase Cγ1. Mol Med Rep. 2016; 14(3): 2457-2464.
|
| [37] |
Zhang GZ, Liu MQ, Chen HW, et al. NF-κB signalling pathways in nucleus pulposus cell function and intervertebral disc degeneration. Cell Prolif. 2021; 54(7):e13057.
|
| [38] |
He R, Wang Z, Cui M, et al. HIF1A alleviates compression-induced apoptosis of nucleus pulposus derived stem cells via upregulating autophagy. Autophagy. 2021; 17(11): 3338-3360.
|
| [39] |
Jia C, Xiang Z, Zhang P, et al. Selenium-SelK-GPX4 axis protects nucleus pulposus cells against mechanical overloading-induced ferroptosis and attenuates senescence of intervertebral disc. Cell Mol Life Sci. 2024; 81(1): 49.
|
| [40] |
Yang S, Zhang F, Ma J, Ding W. Intervertebral disc ageing and degeneration: the antiapoptotic effect of oestrogen. Ageing Res Rev. 2020; 57:100978.
|
| [41] |
Liu S, Yang SD, Huo XW, Yang DL, Ma L, Ding WY. 17β-estradiol inhibits intervertebral disc degeneration by down-regulating MMP-3 and MMP-13 and up-regulating type II collagen in a rat model. Artif Cells Nanomed Biotechnol. 2018; 46(sup2): 182-191.
|
RIGHTS & PERMISSIONS
2026 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.