scholarly journals Evaluation of apoptotic cell death in normal and chondrodystrophic canine intervertebral discs

2012 ◽  
Vol 2 (1) ◽  
pp. 6 ◽  
Author(s):  
Marie Klauser ◽  
Franck Forterre ◽  
Marcus Doherr ◽  
Andreas Zurbriggen ◽  
David Spreng ◽  
...  

Disc degeneration occurs commonly in dogs. A variety of factors is thought to contribute an inappropriate disc matrix that isolate cells in the disc and lead to apoptosis. Disc herniation with radiculopathy and discogenic pain are the results of the degenerative process. The objective of this prospective study was to determine the extent of apoptosis in intact and herniated intervertebral discs of chondrodystrophic dogs and non-chondrodystrophic dogs. In addition, the nucleus pulposus (NP) was histologically compared between non-chondrodystrophic and chondrodystrophic dogs. Thoracolumbar intervertebral discs and parts of the extruded nucleus pulposus were harvested from 45 dogs. Samples were subsequently stained with haematoxylin-eosin and processed to detect cleaved caspase-3 and poly(ADP-ribose) polymerase. A significant greater degree of apoptosis was observed in herniated NPs of chondrodystrophic dogs compared to non- chondrodystrophic dogs with poly (ADP-ribose) polymerase and cleaved caspase- 3 detection. Within the group of chondrodystrophic dogs, dogs with an intact disc and younger than 6 years showed a significant lower incidence of apoptosis in the NP compared to the herniated NP of chondrodystrophic dogs. The extent of apoptosis in the annulus fibrosus was not different between the intact disc from chondrodystrophic and non- chondrodystrophic dogs. An age-related increase of apoptotic cells in NP and annulus fibrosus was found in the intact non-herniated intervertebral discs. Histologically, absence of notochordal cells and occurrence of chondroid metaplasia were observed in the nucleus pulposus of chondrodystrophic dogs. As a result, we found that apoptosis plays a role in disc degeneration in chondrodystrophic dogs.

2018 ◽  
Vol 55 (3) ◽  
pp. 442-452 ◽  
Author(s):  
Wilhelmina Bergmann ◽  
Niklas Bergknut ◽  
Stefanie Veraa ◽  
Andrea Gröne ◽  
Hans Vernooij ◽  
...  

Equine intervertebral disc degeneration is thought to be rare and of limited clinical relevance, although research is lacking. To objectively assess pathological changes of the equine intervertebral disc and their clinical relevance, description of the normal morphology and a practical, biologically credible grading scheme are needed. The objectives of this study are to describe the gross and histological appearance of the equine intervertebral discs and to propose a grading scheme for macroscopic degeneration. Spinal units from 33 warmblood horses were grossly analyzed and scored. Of the 286 intervertebral discs analyzed, 107 (37%) were assigned grade 1 and grade 2 (considered normal) and were analyzed histologically. A nucleus pulposus and an annulus fibrosus could be identified macroscopically and histologically. Histologically, the nucleus pulposus was composed of a cartilaginous matrix and the annulus fibrosus of parallel collagenous bands. A transition zone was also histologically visible. Intra- and inter-observer reliability scores were high for all observers. Higher grades were associated with greater age. Gross changes associated with equine intervertebral disc degeneration (grades 3–5)—that is, yellow discoloration, cleft formation (tearing), and changes in consistency of the nucleus pulposus—were largely similar to those in humans and dogs and were most prevalent in the caudal cervical spine. Equine intervertebral disc degeneration was not associated with osteophyte formation. Changes of the vertebral bone were most common in the thoracolumbar spine but were not correlated with higher grades of intervertebral disc degeneration. Thus, changes of the vertebral bone should be excluded from grading for equine intervertebral disc degeneration.


Polymers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1151 ◽  
Author(s):  
Runze Zhao ◽  
Wanqian Liu ◽  
Tingting Xia ◽  
Li Yang

Low back pain (LBP), commonly induced by intervertebral disc degeneration, is a lumbar disease with worldwide prevalence. However, the mechanism of degeneration remains unclear. The intervertebral disc is a nonvascular organ consisting of three components: Nucleus pulposus, annulus fibrosus, and endplate cartilages. The disc is structured to support our body motion and endure persistent external mechanical pressure. Thus, there is a close connection between force and intervertebral discs in LBP. It is well established that with aging, disordered mechanical stress profoundly influences the fate of nucleus pulposus and the alignment of collagen fibers in the annulus fibrosus. These support a new understanding that disordered mechanical stress plays an important role in the degeneration of the intervertebral discs. Tissue-engineered regenerative and reparative therapies are being developed for relieving disc degeneration and symptoms of lower back pain. In this paper, we will review the current literature available on the role of disordered mechanical stress in intervertebral disc degeneration, and evaluate the existing tissue engineering treatment strategies of the current therapies.


Author(s):  
John McMorran ◽  
Diane Gregory

Abstract In light of the correlation between chronic back pain and intervertebral disc degeneration, this literature review seeks to illustrate the importance of the hydraulic response across the nucleus pulposus- annulus fibrosus interface, by synthesizing current information regarding injurious biomechanics of the spine, stemming from axial compression. Damage to vertebrae, endplates, the nucleus pulposus, and the annulus fibrosus, can all arise from axial compression, depending on the segment's posture, the manner in which it is loaded, and the physiological state of tissue. Therefore, this movement pattern was selected to illustrate the importance of the bracing effect of a pressurized nucleus pulposus on the annulus fibrosus, and how injuries interrupting support to the annulus fibrosus may contribute to intervertebral disc degeneration.


2017 ◽  
Vol 54 (6) ◽  
pp. 945-952 ◽  
Author(s):  
Tove Hansen ◽  
Lucas A. Smolders ◽  
Marianna A. Tryfonidou ◽  
Björn P. Meij ◽  
Johannes C. M. Vernooij ◽  
...  

Since the seminal work by Hans-Jörgen Hansen in 1952, it has been assumed that intervertebral disc (IVD) degeneration in chondrodystrophic (CD) dogs involves chondroid metaplasia of the nucleus pulposus, whereas in nonchondrodystrophic (NCD) dogs, fibrous metaplasia occurs. However, more recent studies suggest that IVD degeneration in NCD and CD dogs is more similar than originally thought. Therefore, the aim of this study was to compare the histopathology of IVD degeneration in CD and NCD dogs. IVDs with various grades of degeneration (Thompson grade I–III, n = 7 per grade) from both CD and NCD dogs were used (14 CD and 18 NCD dogs, 42 IVDs in total). Sections were scored according to a histological scoring scheme for canine IVD degeneration, including evaluation of the presence of fibrocyte-like cells in the nucleus pulposus. In CD dogs, the macroscopically non-degenerated nucleus pulposus contained mainly chondrocyte-like cells, whereas the non-degenerated nucleus pulposus of NCD dogs mainly contained notochordal cells. The histopathological changes in degenerated discs were similar in CD and NCD dogs and resembled chondroid metaplasia. Fibrocytes were not seen in the nucleus pulposus, indicating that fibrous degeneration of the IVD was not present in any of the evaluated grades of degeneration. In conclusion, intervertebral disc degeneration was characterized by chondroid metaplasia of the nucleus pulposus in both NCD and CD dogs. These results revoke the generally accepted concept that NCD and CD dogs suffer from a different type of IVD degeneration, in veterinary literature often referred to as chondroid or fibroid degeneration, and we suggest that chondroid metaplasia should be used to describe the tissue changes in the IVD in both breed types.


Neurosurgery ◽  
2018 ◽  
Vol 85 (2) ◽  
pp. E350-E359 ◽  
Author(s):  
Ibrahim Hussain ◽  
Stephen R Sloan ◽  
Christoph Wipplinger ◽  
Rodrigo Navarro-Ramirez ◽  
Micaella Zubkov ◽  
...  

AbstractBACKGROUNDOur group has previously demonstrated in vivo annulus fibrosus repair in animal models using an acellular, riboflavin crosslinked, high-density collagen (HDC) gel.OBJECTIVETo assess if seeding allogenic mesenchymal stem cells (MSCs) into this gel yields improved histological and radiographic benefits in an in vivo sheep model of annular injury.METHODSFifteen lumbar intervertebral discs (IVDs) were randomized into 4 groups: intact, injury only, injury + acellular gel treatment, or injury + MSC-seeded gel treatment. Sheep were sacrificed at 6 wk. Disc height index (DHI), Pfirrmann grade, nucleus pulposus area, and T2 relaxation time (T2-RT) were calculated for each IVD and standardized to healthy controls from the same sheep. Quantitative histological assessment was also performed using the Han scoring system.RESULTSAll treated IVDs retained gel plugs on gross assessment and there were no adverse perioperative complications. The MSC-seeded gel treatment group demonstrated statistically significant improvement over other experimental groups in DHI (P = .002), Pfirrmann grade (P < .001), and T2-RT (P = .015). There was a trend for greater Han scores in the MSC-seeded gel-treated discs compared with injury only and acellular gel-treated IVDs (P = .246).CONCLUSIONMSC-seeded HDC gel can be delivered into injured IVDs and maintained safely in live sheep to 6 wk. Compared with no treatment and acellular HDC gel, our data show that MSC-seeded HDC gel improves outcomes in DHI, Pfirrmann grade, and T2-RT. Histological analysis shows improved annulus fibrosus and nucleus pulposus reconstitution and organization over other experimental groups as well.


2004 ◽  
Vol 17 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Anna Csiszar ◽  
Zoltan Ungvari ◽  
Akos Koller ◽  
John G. Edwards ◽  
Gabor Kaley

Previously we demonstrated that aging in coronary arteries is associated with proinflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by enhancing endothelial apoptosis. To test this hypothesis we characterized proapoptotic alterations in the phenotype of coronary arteries of aged (26 mo old) and young (3 mo old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was an approximately fivefold increase in the number of apoptotic endothelial cells. In aged coronary arteries there was an increased expression of TNFα, TNFβ, and caspase 9 (microarray, real-time PCR), as well as increased caspase 9 and caspase 3 activity, whereas expression of TNFR1, TNFα-converting enzyme (TACE), Bcl-2, Bcl-X(L), Bid, Bax, caspase 8, and caspase 3 were unchanged. In vessel culture (18 h) incubation of aged coronary arteries with a TNF blocking antibody or the NO donor S-nitroso-penicillamine (SNAP) decreased apoptotic cell death. Incubation of young arteries with exogenous TNFα increased caspase 9 activity and elicited endothelial apoptosis, which was attenuated by SNAP. Inhibition of NO synthesis in cultured young coronary arteries also induced apoptotic cell death and potentiated the apoptotic effect of TNFα. Thus we propose that age-related upregulation of TNFα and caspase 9 and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to impaired endothelial function and ischemic heart disease in the elderly.


2015 ◽  
Vol 84 (3) ◽  
pp. 157-166
Author(s):  
Witold Woźniak ◽  
Małgorzata Grzymisławska ◽  
Joanna Łupicka ◽  
Małgorzata Bruska ◽  
Adam Piotrowski ◽  
...  

Introduction. In the vast literature concerning the development of the intervertebral discs controversies exist as to the period of differentiation and structure of the nucleus pulposus and annulus fibrosus. These controversies result from different determination of age of the investigated embryos. Aim. Using embryos from departmental collection age of which was established according to international Carnegie staging and expressed in postfertilizational days, the differentiation of the intervertebral discs was traced. Material and methods. Study was performed on 34 embryos at developmental stages 13–23 (32–56 days). Embryos were serially sectioned in sagittal, frontal and horizontal planes. Sections were stained with various histological methods and impregnated with silver.Results. Division of sclerotomes into loose cranial and dense caudal zones (sclerotomites) was observed in embryos aged 32 days (stage 13). The intervertebral disc developed from the dense zone of sclerotome and was well recognized in embryos aged 33 days (stage 14). At the end of fifth week (embryos at stage 15, 36 days) the annulus fibrosus and the nucleus pulposus were seen. The annulus fibrosus differentiated into lateral and medial zones. Within the lateral zone cells were arranged into circular rows. These rows were considered as the first stage of laminar structure. In further developmental stages the laminae occupied both zones of the annulus fibrosus.Conclusions. The intervertebral discs develop from the dense zone of the sclerotome which is evident in embryos at stage 13 (32 days). Discs differentiate in embryos aged 33 days, when the nucleus pulposus and annulus fibrosus are recognized. In embryos aged 36 days in the annulus fibrosus circular rows forming laminar arrangement are seen.


2002 ◽  
Vol 30 (6) ◽  
pp. 874-878 ◽  
Author(s):  
E. Thonar ◽  
H. An ◽  
K. Masuda

Intervertebral disc cells cultured in alginate gel are capable of reforming in alginate, a matrix that consists of two compartments: a rim of metabolically active cell-associated matrix and a more abundant, but metabolically less active, further removed matrix. At any one age and in most species, the cell-associated matrix formed by a nucleus pulposus or annulus fibrosus cell cultured in this way is less abundant than that formed by an articular chondrocyte. In both the cell-associated matrix and further removed matrix, the ratio of aggrecan to collagen is significantly higher in the case of nucleus pulposus than of annulus fibrosus, a feature that also distinguishes the matrices of the nucleus pulposus and annulus fibrosus in vivo. Nucleus pulposus and annulus fibrosus cells from older donors show a decreased ability to reform a cell-associated matrix rich in aggrecan. There is, however, some evidence that gene therapy and/or exposure of the cells to defined stimulatory factors can help overcome some of these age-related limitations. This contention is supported by recent evidence that nucleus pulposus and annulus fibrosus cells from adult donors can be manipulated to form, using the recently developed alginate-recovered chondrocyte system, a resilient tissue that bears many of the characteristics of the tissue in which these cells reside in vivo.


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