Genetic murine models of spinal development and degeneration provide valuable insights into intervertebral disc pathobiology

Melrose, James; Tessier, Steven; Risbud, Makarand V.

doi:10.22203/ecm.v041a05

Cited by 4 publications

(21 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Histopathological and structural changes in the IVD are crucial outcome measures due to their effect on IVD function. The mouse as a preclinical model to understand the structure‐function relationship of the IVD has gained importance primarily due to the relevant genetic and behavioral approaches for elucidating the mechanisms of IVD pathologies 16,17 . This study aimed to develop a comprehensive but easy to adapt mouse IVD histopathological scoring criterion, which captures the degenerated features noted in pathological human IVD tissues.…”

Section: Discussionmentioning

confidence: 99%

“…The mouse as a preclinical model to understand the structure-function relationship of the IVD has gained importance primarily due to the relevant genetic and behavioral approaches for elucidating the mechanisms of IVD pathologies. 16,17 This study aimed to develop a comprehensive but easy to adapt mouse IVD histopathological scoring criterion, which captures the degenerated features noted in pathological human IVD tissues. This system enables better cross-study comparison of mouse models, and is sensitive to quantify histopathology in mouse models of IVD degeneration and regeneration.…”

Section: Discussionmentioning

confidence: 99%

“…With the widespread use of mice as a preclinical animal model to understand IVD pathologies (reviewed in References 16 and 17), it is crucial to establish an effective histopathological scoring system that can capture the key known features of human IVD pathologies found in various mouse IVD degeneration models, enabling better cross‐study comparisons. This study aims to develop a comprehensive mouse IVD histopathological scoring system that evaluates histopathology in all regions of mouse IVDs with high sensitivity and specificity to allow cross‐comparison between different mouse models of IVD degeneration and regeneration.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Development of a standardized histopathology scoring system using machine learning algorithms for intervertebral disc degeneration in the mouse model—An ORS spine section initiative

et al. 2021

View full text Add to dashboard Cite

Mice have been increasingly used as preclinical model to elucidate mechanisms and test therapeutics for treating intervertebral disc degeneration (IDD). Several intervertebral disc (IVD) histological scoring systems have been proposed, but none exists that reliably quantitate mouse disc pathologies. Here, we report a new robust quantitative mouse IVD histopathological scoring system developed by building consensus from the spine community analyses of previous scoring systems and features noted on different mouse models of IDD. The new scoring system analyzes 14 key histopathological features from nucleus pulposus (NP), annulus fibrosus (AF), endplate (EP), and AF/NP/EP interface regions. Each feature is categorized and scored; hence, the weight for quantifying the Itzel Paola Melgoza and Srish S. Chenna contributed equally to this work

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Development of a standardized histopathology scoring system using machine learning algorithms for intervertebral disc degeneration in the mouse model—An ORS spine section initiative

et al. 2021

View full text Add to dashboard Cite

show abstract

“…This is reflected in the large number of mouse studies which have been conducted in the last decade to elucidate the multifactorial components that contribute to IVDD. 79 …”

Section: Small Animal Models Of Ivddmentioning

confidence: 99%

“… 83 These models have been an invaluable resource in determining the potential roles of specific genes in human diseases. 79 …”

Section: Small Animal Models Of Ivddmentioning

confidence: 99%

An update on animal models of intervertebral disc degeneration and low back pain: Exploring the potential of artificial intelligence to improve research analysis and development of prospective therapeutics

et al. 2023

View full text Add to dashboard Cite

Animal models have been invaluable in the identification of molecular events occurring in and contributing to intervertebral disc (IVD) degeneration and important therapeutic targets have been identified. Some outstanding animal models (murine, ovine, chondrodystrophoid canine) have been identified with their own strengths and weaknesses. The llama/alpaca, horse and kangaroo have emerged as new large species for IVD studies, and only time will tell if they will surpass the utility of existing models. The complexity of IVD degeneration poses difficulties in the selection of the most appropriate molecular target of many potential candidates, to focus on in the formulation of strategies to effect disc repair and regeneration. It may well be that many therapeutic objectives should be targeted simultaneously to effect a favorable outcome in human IVD degeneration. Use of animal models in isolation will not allow resolution of this complex issue and a paradigm shift and adoption of new methodologies is required to provide the next step forward in the determination of an effective repairative strategy for the IVD. AI has improved the accuracy and assessment of spinal imaging supporting clinical diagnostics and research efforts to better understand IVD degeneration and its treatment. Implementation of AI in the evaluation of histology data has improved the usefulness of a popular murine IVD model and could also be used in an ovine histopathological grading scheme that has been used to quantify degenerative IVD changes and stem cell mediated regeneration. These models are also attractive candidates for the evaluation of novel anti‐oxidant compounds that counter inflammatory conditions in degenerate IVDs and promote IVD regeneration. Some of these compounds also have pain‐relieving properties. AI has facilitated development of facial recognition pain assessment in animal IVD models offering the possibility of correlating the potential pain alleviating properties of some of these compounds with IVD regeneration.

show abstract

Intervertebral disc degeneration and how it leads to low back pain

Diwan

Melrose

2022

JOR Spine

View full text Add to dashboard Cite

The purpose of this review was to evaluate data generated by animal models of intervertebral disc (IVD) degeneration published in the last decade and show how this has made invaluable contributions to the identification of molecular events occurring in and contributing to pain generation. IVD degeneration and associated spinal pain is a complex multifactorial process, its complexity poses difficulties in the selection of the most appropriate therapeutic target to focus on of many potential candidates in the formulation of strategies to alleviate pain perception and to effect disc repair and regeneration and the prevention of associated neuropathic and nociceptive pain. Nerve ingrowth and increased numbers of nociceptors and mechanoreceptors in the degenerate IVD are mechanically stimulated in the biomechanically incompetent abnormally loaded degenerate IVD leading to increased generation of low back pain. Maintenance of a healthy IVD is, thus, an important preventative measure that warrants further investigation to preclude the generation of low back pain. Recent studies with growth and differentiation factor 6 in IVD puncture and multi‐level IVD degeneration models and a rat xenograft radiculopathy pain model have shown it has considerable potential in the prevention of further deterioration in degenerate IVDs, has regenerative properties that promote recovery of normal IVD architectural functional organization and inhibits the generation of inflammatory mediators that lead to disc degeneration and the generation of low back pain. Human clinical trials are warranted and eagerly anticipated with this compound to assess its efficacy in the treatment of IVD degeneration and the prevention of the generation of low back pain.

show abstract

Genetic murine models of spinal development and degeneration provide valuable insights into intervertebral disc pathobiology

Cited by 4 publications

References 88 publications

Development of a standardized histopathology scoring system using machine learning algorithms for intervertebral disc degeneration in the mouse model—An ORS spine section initiative

Development of a standardized histopathology scoring system using machine learning algorithms for intervertebral disc degeneration in the mouse model—An ORS spine section initiative

An update on animal models of intervertebral disc degeneration and low back pain: Exploring the potential of artificial intelligence to improve research analysis and development of prospective therapeutics

Intervertebral disc degeneration and how it leads to low back pain

Contact Info

Product

Resources

About