Physical disruption of intervertebral disc promotes cell clustering and a degenerative phenotype
| Autor: | Trish Dolan, IJ Harding, Michael A. Adams, Christine L. Le Maitre, Polly Lama, Luke Flower, Harry Claireaux |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Immunology Integrin Diseases Caspase 3 Matrix (biology) Matrix metalloproteinase lcsh:RC254-282 Article Glycosaminoglycan 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine In vivo medicine lcsh:QH573-671 Integrin binding biology lcsh:Cytology Chemistry Intervertebral disc Cell Biology lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell biology 030104 developmental biology medicine.anatomical_structure biology.protein Molecular modelling 030217 neurology & neurosurgery |
| Zdroj: | Cell Death Discovery Cell Death Discovery, Vol 5, Iss 1, Pp 1-9 (2019) |
| ISSN: | 2058-7716 |
| DOI: | 10.1038/s41420-019-0233-z |
| Popis: | To test the hypothesis that physical disruption of an intervertebral disc disturbs cell-matrix binding, leading to cell clustering and increased expression of matrix degrading enzymes that contribute towards degenerative disc cell phenotype. Lumbar disc tissue was removed at surgery from 21 patients with disc herniation, 11 with disc degeneration, and 8 with adolescent scoliosis. 5 μm sections were examined with histology, and 30-µm sections by confocal microscopy. Antibodies were used against integrin α5beta1, matrix metalloproteinases (MMP) 1, MMP-3, caspase 3, and denatured collagen types I and II. Spatial associations were sought between cell clustering and various degenerative features. An additional, 11 non-herniated human discs were used to examine causality: half of each specimen was cultured in a manner that allowed free ‘unconstrained’ swelling (similar to a herniated disc in vivo), while the other half was cultured within a perspex ring that allowed ‘constrained’ swelling. Changes were monitored over 36 h using live-cell imaging. 1,9-Di-methyl methylene blue (DMMB) assay for glycosaminoglycan loss was carried out from tissue medium. Partially constrained specimens showed little swelling or cell movement in vitro. In contrast, unconstrained swelling significantly increased matrix distortion, glycosaminoglycan loss, exposure of integrin binding sites, expression of MMPs 1 and 3, and collagen denaturation. In the association studies, herniated disc specimens showed changes that resembled unconstrained swelling in vitro. In addition, they exhibited increased cell clustering, apoptosis, MMP expression, and collagen denaturation compared to ‘control’ discs. Results support our hypothesis. Further confirmation will require longitudinal animal experiments. |
| Databáze: | OpenAIRE |
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