# Establishment and research progress of animal models for intervertebral disc degeneration

**Authors:** Cong Zhang, Rui Sun, Qing Jiang

PMC · DOI: 10.1515/biol-2025-1295 · Open Life Sciences · 2026-03-02

## TL;DR

This review summarizes current animal models for studying intervertebral disc degeneration and highlights challenges and future directions to improve research and treatment development.

## Contribution

The paper provides a systematic synthesis of existing IDD animal models and outlines future research directions to enhance translational outcomes.

## Key findings

- Current IDD animal models include injury, spontaneous, mechanical, and chemical models with distinct advantages and limitations.
- Existing models struggle to replicate the progressive and heterogeneous nature of human IDD.
- Advances in bioengineering and molecular imaging offer new opportunities for improved model development and evaluation.

## Abstract

Low back pain associated with intervertebral disc degeneration (IDD) is a prevalent condition in clinical practice, significantly impacting patients’ work and quality of life. Animal models are indispensable for IDD research, offering crucial tools to investigate the molecular mechanisms of disease onset and progression, as well as to evaluate potential therapeutic interventions. Current animal models for IDD include intervertebral disc injury, spontaneous degeneration, mechanically induced, and chemically induced models, each exhibiting unique strengths and limitations in mimicking the pathological features of human IDD. Despite these advancements, existing models continue to struggle with replicating the long-term, progressive nature of degeneration and the heterogeneity observed in human patients. With the emergence of bioengineering techniques and molecular imaging, novel approaches to model construction and evaluation have opened new avenues for IDD research. This review systematically synthesizes current strategies for constructing IDD animal models, their application characteristics, and associated challenges, while also projecting future research directions. The aim is to provide guidance for optimizing model selection and accelerating translational research in the field of IDD.

## Linked entities

- **Diseases:** intervertebral disc degeneration (MONDO:0011385)

## Full-text entities

- **Genes:** Piezo1 (piezo-type mechanosensitive ion channel component 1) [NCBI Gene 234839] {aka 9630020g22, Fam38a, mKIAA0233}, Cxcl15 (C-X-C motif chemokine ligand 15) [NCBI Gene 20309] {aka Il8, Scyb15, lungkine, weche}, Rela (Rela proto-oncogene, NFKB subunit) [NCBI Gene 19697] {aka p65, p65 NF-kappa B, p65 NFkB}, Mmp13 (matrix metallopeptidase 13) [NCBI Gene 17386] {aka Clg, MMP-13, Mmp1}, ACAN (aggrecan) [NCBI Gene 176] {aka AGC1, AGCAN, CSPG1, CSPGCP, MSK16, SEDK}, Hif1a (hypoxia inducible factor 1, alpha subunit) [NCBI Gene 15251] {aka HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Col2a1 (collagen, type II, alpha 1) [NCBI Gene 12824] {aka Col2, Col2a, Col2a-1, Del1, Dmm, Lpk}, ADAMTS4 (ADAM metallopeptidase with thrombospondin type 1 motif 4) [NCBI Gene 9507] {aka ADAMTS-2, ADAMTS-4, ADMP-1}, Fn1 (fibronectin 1) [NCBI Gene 14268] {aka E330027I09, Fn, Fn-1}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, Sparc (secreted acidic cysteine rich glycoprotein) [NCBI Gene 20692] {aka BM-40, ON}, Idd2 (insulin dependent diabetes susceptibility 2) [NCBI Gene 110654] {aka Idd-2}, MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314] {aka CHDS6, MMP-3, SL-1, STMY, STMY1, STR1}, Tnmd (tenomodulin) [NCBI Gene 64103] {aka 1110017I01Rik, Bricd4, ChM1L, TeM}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}
- **Diseases:** Muscle tissue damage (MESH:D009379), cold hypersensitivity (MESH:C569627), Spinal instability (MESH:D043171), CEP hyperplasia (MESH:D006965), motor impairment (MESH:D000068079), type 2 diabetes (MESH:D003924), degeneration and necrosis of (MESH:D009410), anterior disc injury (MESH:D055959), AF (OMIM:614822), hypersensitivity (MESH:D004342), infection (MESH:D007239), posterior instability2 (MESH:D001041), embryonic death (MESH:D003643), Intervertebral disc injury (MESH:C535531), back pain (MESH:D001416), metabolic disorders (MESH:D008659), neurological dysfunction (MESH:D009461), spinal instability2 (MESH:D013122), acute injury2 (MESH:D000208), Low back pain (MESH:D017116), intervertebral disc herniation (MESH:D007405), NP (MESH:C537927), hypoxia (MESH:D000860), CEP (MESH:D002357), lumbar instability (MESH:C563613), swelling (MESH:D004487), inflammation (MESH:D007249), degenerative disease (MESH:D019636), leg pain (MESH:D010146)
- **Chemicals:** pNIPAAm (MESH:C052970), adenosine triphosphate (MESH:D000255), lipopolysaccharide (MESH:D008070), serpentine (MESH:C009244), anhydrous alcohol (-), glycosaminoglycan (MESH:D006025), pingyangmycin (MESH:C025703), water (MESH:D014867), monosodium iodoacetate (MESH:D019807), sugar (MESH:D000073893), alginate (MESH:D000464)
- **Species:** Capra hircus (domestic goat, species) [taxon 9925], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Bos taurus (bovine, species) [taxon 9913], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Macaca mulatta (rhesus macaque, species) [taxon 9544], Sus scrofa (pig, species) [taxon 9823], Nicotiana tabacum (American tobacco, species) [taxon 4097], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

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## References

69 references — full list in the complete paper: https://tomesphere.com/paper/PMC12952208/full.md

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Source: https://tomesphere.com/paper/PMC12952208