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

Melgoza, Itzel Paola; Chenna, Srish S.; Tessier, Steven; Zhang, Yejia; Tang, Simon Y.; Ohnishi, Takashi; Novais, Emanuel J.; Kerr, Geoffrey J.; Mohanty, Sarthak; Tam, Vivian; Chan, Wing‐Lok; Zhou, Chao; Zhang, Ying; Leung, Victor; Brice, Alexis; Séguin, Cheryle A.; Chan, Danny; Vo, Nam; Risbud, Makarand V.; Dahia, Chitra Lekha

doi:10.1002/jsp2.1164

Cited by 46 publications

(50 citation statements)

References 53 publications

(131 reference statements)

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“…Although LSI model developed more calcification in the lower EP, with oral administration of PNS, especially with medium dose (PNS‐M, 80 mg/kg/d), porosity of the EP and formation of bone marrow cavities in sclerotic EP were reduced significantly (Figure 4B‐E ). In line with a quantitative mouse IVD histopathological scoring system previously described to evaluate the whole degenerative IVD, 29 we scored the NP, AF, EP, and AF/NP/EP boundary regions in every single IVD of each group. The combined IVD score showed that all of the LSI operation groups had a significant higher score than the sham operation group, while the PNS‐M‐treated group scored slightly lower than the LSI group (Figure 4F ).…”

Section: Resultsmentioning

confidence: 99%

“…And then, we applied a quantitative mouse IVD histopathological scoring system to evaluate the IDD from Safranin O‐Fast Green sections. 29 The scoring system analyzed 14 key histopathological features from NP, AF, EP, and AF/NP/EP interface regions. The total score ranges from 0 to 36, classifying normal (0‐6), mild (7‐13), moderate (14‐25), and severe IDD (26‐35).…”

Section: Methodsmentioning

confidence: 99%

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Panax notoginseng saponins attenuate intervertebral disc degeneration by reducing the end plate porosity in lumbar spinal instability mice

Chang

Huang

et al. 2021

JOR Spine

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Although painkillers could alleviate some of the symptoms, there are no drugs that really cope with the intervertebral disc degeneration (IDD) at present, so it is urgent to find a cure that could prevent or reverse the progression of IDD. During the development of IDD, the cartilaginous end plates (EPs) become hypertrophic and porous by the increase of osteoclast activities, which hinder the penetration of nutrition. The compositional and structural degeneration of the EP may cause both nutritional as well as mechanical impairment to the nucleus pulposus (NP) so that developing drugs that target the degenerating EP may be another option in addition to targeting the NP. In the lumbar spine instability mouse model, we found increased porosity in the cartilaginous EP, accompanied by the decrease in total intervertebral disc volume.Panax notoginseng saponins (PNS), a traditional Chinese patent drug with antiosteoclastogenesis effect, could alleviate IDD by inhibiting aberrant osteoclast activation in the porous EP. Further in vitro experiment validated that PNS inhibit the receptor activator of nuclear factor kappa-Β ligand-induced osteoclast differentiation, while the transcriptional activation of PAX6 may be involved in the mechanism, which had been defined as an inhibitory transcription factor in osteoclastogenesis.These findings may provide a novel therapeutic strategy for IDD.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Panax notoginseng saponins attenuate intervertebral disc degeneration by reducing the end plate porosity in lumbar spinal instability mice

Chang

Huang

et al. 2021

JOR Spine

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Section: The Intervertebral Discmentioning

confidence: 99%

“…This review focuses on the nucleus pulposus cells of the human IVD. For representative examples of the other species used in disc (patho)biology the reader is referred to the recent series of a multi-species histopathological grading schemes reported for mice (Melgoza et al, 2021), rats (Lai et al, 2021), rabbits (Gullbrand et al, 2021), large animal (Lee et al, 2021) the role of genetics and specific genes in NCs towards NPC transition, as well as the use of live-cell imaging technology to monitor this transition (Joo Han . These fundamental and mechanistic studies involving mice will not only shed light on NC (patho)physiology but will also assist in further identifying and confirming cell markers for the specific life-stages of NCs; its journey from the notochord to the disc and its role during maturation and ageing.…”

Section: Mouse Modelsmentioning

confidence: 99%

Notochordal Cell-Based Treatment Strategies and Their Potential in Intervertebral Disc Regeneration

Bach

Poramba‐Liyanage

Riemers

et al. 2022

Front. Cell Dev. Biol.

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Chronic low back pain is the number one cause of years lived with disability. In about 40% of patients, chronic lower back pain is related to intervertebral disc (IVD) degeneration. The standard-of-care focuses on symptomatic relief, while surgery is the last resort. Emerging therapeutic strategies target the underlying cause of IVD degeneration and increasingly focus on the relatively overlooked notochordal cells (NCs). NCs are derived from the notochord and once the notochord regresses they remain in the core of the developing IVD, the nucleus pulposus. The large vacuolated NCs rapidly decline after birth and are replaced by the smaller nucleus pulposus cells with maturation, ageing, and degeneration. Here, we provide an update on the journey of NCs and discuss the cell markers and tools that can be used to study their fate and regenerative capacity. We review the therapeutic potential of NCs for the treatment of IVD-related lower back pain and outline important future directions in this area. Promising studies indicate that NCs and their secretome exerts regenerative effects, via increased proliferation, extracellular matrix production, and anti-inflammatory effects. Reports on NC-like cells derived from embryonic- or induced pluripotent-stem cells claim to have successfully generated NC-like cells but did not compare them with native NCs for phenotypic markers or in terms of their regenerative capacity. Altogether, this is an emerging and active field of research with exciting possibilities. NC-based studies demonstrate that cues from developmental biology can pave the path for future clinical therapies focused on regenerating the diseased IVD.

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“…Assessment of IVD degeneration: Histological classification system recently developed by Melgoza et al in 2021 was used to quantify the degeneration of the injured level (L6/S1) which allows the independent evaluation of the nucleus pulposus, annulus fibrosus, endplates and interface boundaries 19 .…”

Section: Measuring Thickness Of Af and The Depth Of Partial-width Injurymentioning

confidence: 99%

Contrast-enhanced microCT evaluation of degeneration following partial and full width injuries to mouse lumbar intervertebral disc

Walk

Moon

Tang

et al. 2022

Preprint

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Study Design: Preclinical animal study. Objective: Evaluation of the degenerative progression resulting from either a partial- or full- width injury to the mouse lumbar intervertebral disc (IVD) using contrast-enhanced micro-computed tomography and histological analyses. We utilized a lateral-retroperitoneal surgical approach to access the lumbar IVD, and the injuries to the IVD were induced by either incising one side of the annulus fibrosus or puncturing both sides of the annulus fibrosus. The full-width injury caused dramatic reduction in nucleus pulposus hydration and significant degeneration. A partial-width injury produces localized deterioration around the annulus fibrosus site that resulted in local tissue remodeling without gross degeneration to the IVD. Methods: Female C57BL/6J mice of 3-4 months age were used in this study. They were divided into three groups to undergo a partial-width, full-width, or sham injuries. The L5/L6 and L6/S1 lumbar IVDs were surgically exposed using a lateral-retroperitoneal approach. The L6/S1 IVDs were injured using either a surgical scalpel (partial-width) or a 33G needle (full-width), with the L5/L6 serving as an internal control. These animals were allowed to recover and then sacrificed at 2-, 4-, or 8- weeks post-surgery. The IVDs were assessed for degeneration using contrast-enhanced microCT (CEμCT) and histological analysis. Results: The high-resolution 3D evaluation of the IVD confirmed that the respective injuries localized within one side of the annulus fibrosus or spanned the full width of the IVD. The full-width injury caused deteriorations in the nucleus pulposus after 2 weeks that culminated in significant degeneration at 8 weeks, while the partial width injury caused localized disruptions that remained limited to the annulus fibrosus. Conclusion: The use of CEμCT revealed distinct IVD degeneration profiles resulting from partial- and full- width injuries. The partial width injury may serve as a better model for IVD degeneration resulting from localized annulus fibrosus injuries in humans.

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

Cited by 46 publications

References 53 publications

Panax notoginseng saponins attenuate intervertebral disc degeneration by reducing the end plate porosity in lumbar spinal instability mice

Panax notoginseng saponins attenuate intervertebral disc degeneration by reducing the end plate porosity in lumbar spinal instability mice

Notochordal Cell-Based Treatment Strategies and Their Potential in Intervertebral Disc Regeneration

Contrast-enhanced microCT evaluation of degeneration following partial and full width injuries to mouse lumbar intervertebral disc

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