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- Inkinen, Ritva, et al.
(författare)
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Relative increase of biglycan and decorin and altered chondroitin sulfate epitopes in the degenerating human intervertebral disc.
- 1998
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 25:3, s. 506-514
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Proteoglycans are major components of the extracellular matrix of the intervertebral disc. They are vital for the biomechanical properties of the tissue, and are subject to changes in disc degeneration. We aimed to further define these changes and their relationship to normal aging.METHODS: Normal discs (age 13-53 years, n = 6) were analyzed from 5 different sites across the sagittal anterior-posterior direction. Degenerated anterior annulus fibrosus was collected from 7 patients aged 39-46 years. Extracted proteoglycans were separated using agarose and polyacrylamide gel electrophoresis and detected with toluidine blue staining and Western blotting.RESULTS: The center of the disc showed the highest level of total proteoglycans, but lowest levels of decorin and biglycan. Western blots displayed reduced signal for both glycanated and nonglycanated biglycan and decorin after adolescence, while an increased signal of biglycan was observed in degenerated annuli. The 7D4(-) and 3B3(-) epitopes on native chondroitin sulfate chains were present in the large proteoglycans of intervertebral discs, but their signal intensity had no correlation to degeneration. Chondroitinase ABC digestion of the blots brought up 7D4(+) signal in the small proteoglycans of degenerated, but not in healthy tissue. Decrease or total loss of 2B6(+) epitope (indicating 4-sulfated stubs of chondroitin sulfate chains) were found in the large proteoglycans of all degenerated annuli.CONCLUSION: Human intervertebral disc degeneration involves the accumulation of decorin and biglycan relative to other uronic acid containing proteoglycans, the disappearance of 4-sulfated core region in aggrecan-like large proteoglycans, and the emergence of a core structure in the chains of small proteoglycans reacting with the 7D4 antibody; these findings indicate a fundamental alteration in matrix properties that may contribute to the pathogenesis of the disease.
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| 2. |
- Karppinen, Jaro, et al.
(författare)
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Effects of tiaprofenic acid and indomethacin on proteoglycans in the degenerating porcine intervertebral disc.
- 1995
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Ingår i: Spine. - : Wolters Kluwer. - 0362-2436 .- 1528-1159. ; 20:10, s. 1170-1177
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: Eighteen pigs were stabbed with a scalpel in the anterior part of the anulus fibrosus of a lumbar disc. After surgery, the pigs received either tiaprofenic acid or indomethacin daily, and a third group did not receive any medication.OBJECTIVES: Nonsteroidal anti-inflammatory agents are widely used in the treatment of low back patients, but their long-term effects on the matrix molecules in the degenerate disc are unknown.SUMMARY OF BACKGROUND DATA: Several in vitro and in vivo studies on articular cartilage have suggested that tiaprofenic acid may not have adverse effects on matrix metabolism, whereas indomethacin probably does.METHODS: Uronic acid, DNA, and water contents were determined from five different locations in each injured disc. Transport and incorporation of sulfate were examined by in vivo radioactive tracer analysis, and proteoglycan structures were analyzed by gel electrophoresis.RESULTS: Morphologically, there were no differences between the treatments. Tiaprofenic acid maintained a higher uronic acid content in the nucleus pulposus and outer anulus compared with that of the nonmedicated animals. Tiaprofenic acid decreased the incorporation of sulfate in the injured area and the water content at most sites. Indomethacin had no adverse effects compared with the nonmedicated group, and it increased water content in the posterior anulus fibrosus.CONCLUSIONS: Long-term administration of tiaprofenic acid and indomethacin did not have harmful effects on matrix metabolism after disc injury. On the contrary, tiaprofenic acid may slightly protect proteoglycans in the degenerating disc.
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| 3. |
- Kääpä, Eeva, et al.
(författare)
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Elevated protein content and prolyl 4-hydroxylase activity in severely degenerated human annulus fibrosus.
- 2000
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Ingår i: Connective Tissue Research. - : Informa Healthcare. - 0300-8207 .- 1607-8438. ; 41:2, s. 93-99
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Tidskriftsartikel (refereegranskat)abstract
- Alterations involved with the intervertebral disc degeneration are partly well described, however, it is not so well known how collagen network is affected by the disease. We analyzed the rate of collagen biosynthesis (estimated by the enzymic activities of prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase) and the level of hydroxylysylpyridinoline and lysylpyridinoline crosslinks both in normal (n=7) and degenerated (n=7) human annulus fibrosus. The activity of prolyl 4-hydroxylase was significantly increased in degenerated tissue. However, no significant changes in the collagen content or in the amount of hydroxylysylpyridinoline and lysylpyridinoline collagen crosslinks were observed. On the other hand, the content of soluble proteins was significantly increased. Our results suggest that collagen biosynthesis is increased in degenerated human annulus fibrosus, obviously to compensate the impairment of collagen fibers. The faster turnover of collagen in degenerated annulus fibrosus, suggested by the increased prolyl 4-hydroxylase activity and unchanged collagen content, seems not to cause any significant changes in its mature pyridinium crosslink concentrations.
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| 4. |
- Kääpä, Eeva, et al.
(författare)
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Proteoglycan chemistry in experimentally injured porcine intervertebral disk.
- 1994
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Ingår i: Journal of spinal disorders. - : Lippincott Williams & Wilkins. - 0895-0385 .- 1531-2305. ; 7:4, s. 296-306
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Tidskriftsartikel (refereegranskat)abstract
- An animal model of disk degeneration was used to study the concentration levels and types of proteoglycans in the different parts of the intervertebral disk. An annular incision was made with a scalpel blade into the anterior part of the porcine lumbar intervertebral disks via a retroperitoneal approach. Three months after injury the morphology of the injured disk had changed considerably. Disk height was diminished, and in the injured segment osteophytes had formed at the ventral edges of the vertebral body. The nucleus was small, fibrous, and yellowish. The annular lesion had healed by formation of granulation tissue, but the lamellar structure was partially destroyed. The concentration of inorganic [35S]sulfate had decreased across the whole disk, reflecting a decrease in the rate of solute transport. The concentration of incorporated [35S]sulfate had also decreased in the injured disks. The DNA concentration in the anterior annulus and in the nucleus had increased, whereas both the concentration of uronic acid and the ratio of chondroitin-6-sulfate to chondroitin-4-sulfate in the nucleus had decreased. Agarose gel electrophoresis combined with chondroitinase B digestion suggested the presence of dermatan sulfate proteoglycans in the injured annulus fibrosus. The morphology and chemical composition of the disks adjacent to the injured one were normal, and only a slight increase in the concentration of incorporated [35S]sulfate was observed in the disks above the injured one.
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