Molecular Changes in the Degenerated Goat Intervertebral Disc

Hoogendoorn, Roel J. W.; Doulabi, Behrouz Zandieh; Huang, Chun L.; Wuisman, P.; Bank, Ruud A.; Helder, Marco N.

doi:10.1097/brs.0b013e31817d2468

Cited by 31 publications

(23 citation statements)

References 43 publications

(53 reference statements)

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“…This is reflected by the high and low gene expression levels of aggrecan seen in the corresponding freshly isolated (fibro)chondrocytes. Expression levels of ECM-related genes that we found in freshly isolated chondrocytes are comparable to the levels found in goat chondrocytes in situ (Hoogendoorn et al, 2008b). In rats, also no differences were found in the gene expression between RNA extracted from tissue compared to RNA from isolated cells (Lee et al, 2007).…”

Section: Chondrocytes Isolated From Different (Fibro)cartilaginous Tisupporting

confidence: 80%

Caprine articular, meniscus and intervertebral disc cartilage: An integral analysis of collagen network and chondrocytes

et al. 2010

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Section: Chondrocytes Isolated From Different (Fibro)cartilaginous Tisupporting

confidence: 80%

Caprine articular, meniscus and intervertebral disc cartilage: An integral analysis of collagen network and chondrocytes

et al. 2010

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“…47 Increases in catabolic gene expression have also been illustrated in this model with increasing severity of degeneration. 48 Mild to moderate changes to the goat disc have also been reported following surgically induced injury to the annulus, based on histological outcomes. 13,49,50 …”

Section: Discussionmentioning

confidence: 99%

A large animal model that recapitulates the spectrum of human intervertebral disc degeneration

Gullbrand

Malhotra

Schaer

et al. 2017

Osteoarthritis and Cartilage

101

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Objective The objective of this study was to establish a large animal model that recapitulates the spectrum of intervertebral disc degeneration that occurs in humans and which is suitable for pre-clinical evaluation of a wide range of experimental therapeutics. Design Degeneration was induced in the lumbar intervertebral discs of large frame goats by either intradiscal injection of chondroitinase ABC (ChABC) over a range of dosages (0.1U, 1U or 5U) or subtotal nucleotomy. Radiographs were used to assess disc height changes over 12 weeks. Degenerative changes to the discs and endplates were assessed via magnetic resonance imaging (MRI), semi-quantitative histological grading, micro-computed tomography (µCT), and measurement of disc biomechanical properties. Results Degenerative changes were observed for all interventions that ranged from mild (0.1U ChABC) to moderate (1U ChABC and nucleotomy) to severe (5U ChABC). All groups showed progressive reductions in disc height over 12 weeks. Histological scores were significantly increased in the 1U and 5U ChABC groups. Reductions in T2 and T1ρ, and increased Pfirrmann grade were observed on MRI. Resorption and remodeling of the cortical boney endplate adjacent to ChABC injected discs also occurred. Spine segment range of motion was greater and compressive modulus was lower in 1U ChABC and nucleotomy discs compared to intact. Conclusions A large animal model of disc degeneration was established that recapitulates the spectrum of structural, compositional and biomechanical features of human disc degeneration. This model may serve as a robust platform for evaluating the efficacy of therapeutics targeted towards varying degrees of disc degeneration.

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“…Among various enzymes, chondroitinase ABC, trypsin and papain (serine protease) have been used to induce IVD degeneration. Chondroitinase ABC has been widely used to remove painful tissue in disc herniation but was also intensively investigated to induce disc degeneration in vitro and in vivo [101-107] (Table 2). Papain has been repeatedly shown to induce cavity formation if injected in various doses [77,108].…”

Section: Enzymatic Disc Degeneration Modelsmentioning

confidence: 99%

Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

Gantenbein¹,

Illien-Jünger²,

Chan³

et al. 2015

CSCR

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In recent decades the application of bioreactors has revolutionized the concept of culturing tissues and organs that require mechanical loading. In intervertebral disc (IVD) research, collaborative efforts of biomedical engineering, biology and mechatronics have led to the innovation of new loading devices that can maintain viable IVD organ explants from large animals and human cadavers in precisely defined nutritional and mechanical environments over extended culture periods. Particularly in spine and IVD research, these organ culture models offer appealing alternatives, as large bipedal animal models with naturally occurring IVD degeneration and a genetic background similar to the human condition do not exist. Latest research has demonstrated important concepts including the potential of homing of mesenchymal stem cells to nutritionally or mechanically stressed IVDs, and the regenerative potential of “smart” biomaterials for nucleus pulposus or annulus fibrosus repair. In this review, we summarize the current knowledge about cell therapy, injection of cytokines and short peptides to rescue the degenerating IVD. We further stress that most bioreactor systems simplify the real in vivo conditions providing a useful proof of concept. Limitations are that certain aspects of the immune host response and pain assessments cannot be addressed with ex vivo systems. Coccygeal animal disc models are commonly used because of their availability and similarity to human IVDs. Although in vitro loading environments are not identical to the human in vivo situation, 3D ex vivo organ culture models of large animal coccygeal and human lumbar IVDs should be seen as valid alternatives for screening and feasibility testing to augment existing small animal, large animal, and human clinical trial experiments.

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Molecular Changes in the Degenerated Goat Intervertebral Disc

Abstract: Changes in the GAG/Hyp ratio of chemically induced degeneration in goat IVD resemble the changes seen in humans. Gene expression profiles match the pattern of degeneration, suggesting that the injection of chondroitinase ABC might mimic the onset of human disc degeneration.

Cited by 31 publications

References 43 publications

Caprine articular, meniscus and intervertebral disc cartilage: An integral analysis of collagen network and chondrocytes

Caprine articular, meniscus and intervertebral disc cartilage: An integral analysis of collagen network and chondrocytes

A large animal model that recapitulates the spectrum of human intervertebral disc degeneration

Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

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