| 1. |
- Hayes, Anthony J., et al.
(författare)
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Spinal Deformity in Aged Zebrafish Is Accompanied by Degenerative Changes to Their Vertebrae that Resemble Osteoarthritis
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9, s. e75787-
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Tidskriftsartikel (refereegranskat)abstract
- Age-related degenerative changes within the vertebral column are a significant cause of morbidity with considerable socio-economic impact worldwide. An improved understanding of these changes through the development of experimental models may lead to improvements in existing clinical treatment options. The zebrafish is a well-established model for the study of skeletogenesis with significant potential in gerontological research. With advancing age, zebrafish frequently develop gross deformities of their vertebral column, previously ascribed to reduced trunk muscle tone. In this study, we assess degenerative changes specifically within the bone and cartilage of the vertebral column of zebrafish at 1, 2 and 3-years of age. We show increased frequency and severity of spinal deformities/curvatures with age. Underlying the most severe phenotypes are partial or complete vertebral dislocations and focal thickening of the vertebral bone at the joint margins. MicroCT examination demonstrates small defects, fractures and morphological evidence suggestive of bone erosion and remodeling (i.e. osteophytes) within the vertebrae during aging, but no significant change in bone density. Light and electron microscopic examination reveal striking agerelated changes in cell morphology, suggestive of chondroptosis, and tissue remodelling of the vertebral cartilage, particularly within the pericellular micro-environment. Glycosaminoglycan analysis of the vertebral column by HPLC demonstrates a consistent, age-related increase in the yield of total chondroitin sulfate disaccharide, but no change in sulfation pattern, supported by immunohistochemical analysis. Immunohistochemistry strongly identifies all three chondroitin/dermatan sulphate isoforms (C-0-S, C-4-S/DS and C-6-S) within the vertebral cartilage, particularly within the pericellular micro-environment. In contrast, keratan sulfate immunolocalises specifically with the notochordal tissue of the intervertebral disc, and its labelling diminishes with age. In summary, these observations raise the prospect that zebrafish, in addition to modelling skeletal development, may have utility in modelling age-related degenerative changes that affect the skeleton during senescence.
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| 2. |
- Lindahl, Birgitta, et al.
(författare)
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Selective loss of cerebral keratan sulfate in Alzheimer's disease
- 1996
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Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 271:29, s. 16991-16994
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Tidskriftsartikel (refereegranskat)abstract
- Proteoglycans, especially heparan sulfate-substituted species, are known to be associated with the deposition of amyloid in Alzheimer's disease, We previously found that heparan sulfate from afflicted brains, and from control subjects, differed minimally in quantity and structure (Lindahl, B., Eriksson, L., and Lindahl, U. (1995) Biochem, J, 306, 177-184), In the present study, a glyco saminoglycan fraction, shown to contain heparan sulfate and keratan sulfate, was radiolabeled by partial N-deacetylation (hydrazinolysis) followed by re-N-acetylation using [H-3]acetic anhydride, Quantitation of the H-3-labeled polysaccharides, based on digestion with heparitinase I from Flavobacterium heparinum and keratanase from Pseudomonas sp., revealed that the amounts of keratan sulfate in Alzheimer cerebral cortex are reduced to less than half of control values. Moreover, a monoclonal antibody against a highly sulfated keratan sulfate epitope bound to the majority of the neurons in normal cortex but not in the diseased tissue. The lack of highly sulfated keratan sulfate structures may reflect a specific functional defect of the cells.
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| 3. |
- Nandadasa, Sumeda, et al.
(författare)
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Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth
- 2020
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Ingår i: eLife. - 2050-084X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The umbilical artery lumen closes rapidly at birth, preventing neonatal blood loss, whereas the umbilical vein remains patent longer. Here, analysis of umbilical cords from humans and other mammals identified differential arterial-venous proteoglycan dynamics as a determinant of these contrasting vascular responses. The umbilical artery, but not the vein, has an inner layer enriched in the hydrated proteoglycan aggrecan, external to which lie contraction-primed smooth muscle cells (SMC). At birth, SMC contraction drives inner layer buckling and centripetal displacement to occlude the arterial lumen, a mechanism revealed by biomechanical observations and confirmed by computational analyses. This vascular dimorphism arises from spatially regulated proteoglycan expression and breakdown. Mice lacking aggrecan or the metalloprotease ADAMTS1, which degrades proteoglycans, demonstrate their opposing roles in umbilical vascular dimorphism, including effects on SMC differentiation. Umbilical vessel dimorphism is conserved in mammals, suggesting that differential proteoglycan dynamics and inner layer buckling were positively selected during evolution.
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| 4. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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