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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2003 Nov;62(11):1054–1060. doi: 10.1136/ard.62.11.1054

ß Irradiation decreases collagen type II synthesis and increases nitric oxide production and cell death in articular chondrocytes

J Ailland 1, W Kampen 1, M Schunke 1, J Trentmann 1, B Kurz 1
PMCID: PMC1754347  PMID: 14583567

Abstract

Background: When synovitis is proved, intra-articularly injected ß emitting radionuclides like yttrium-90 (90Y) are used to treat the inflamed synovium.

Objective: To study the viability, matrix production, and NO production during or after 90Y treatment of chondrocytes.

Methods: Monolayer, alginate, and explant cultures of primary bovine articular chondrocytes as well as synoviocytes were incubated with 0–3 MBq 90Y/ml medium for four days from culture day 3 onwards. Cell viability was demonstrated by light and electron microscopy or by trypan blue or ethidium bromide/fluorescein diacetate staining, membrane integrity by measurement of lactate dehydrogenase (LDH) activity in the culture supernatants. Biosynthetic activity was demonstrated by incorporation of [3H]proline and immunocytochemical staining of collagen type II. NO production was measured with the Griess reagent.

Results: In chondrocyte and synoviocyte monolayer cultures radiation caused a dose dependent increase in cell death and membrane destruction within four days. In alginate and explant cultures, where proliferation is low, no significantly increased LDH activity was seen, and cell viability was ∼100% for up to 14 days after irradiation. Collagen type II expression (alginate) and biosynthetic activity (alginate and explants) were decreased dose dependently while there was an increase in NO production. Light and electron microscopy data showed that five weeks after irradiation all cells in alginate and most cells in explants subjected to 3 MBq 90Y/ml were dead, whereas after lower amounts of irradiation several morphologically intact cells were found.

Conclusions: ß Irradiation may influence the long term maintenance of cartilage tissue or the aetiology of degenerative joint diseases.

Full Text

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Figure 1 .

Figure 1

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Semi-thin sections (A–D) and electron microscopy (E, F) of cartilage explants (A, B) and primary chondrocytes in alginate (C–F) five weeks after a four day period of ß irradiation indicating an induction of cell destruction. (A, C and E) Control cultures. Arrows demonstrate intact cells in A and C or intact organelles like the nucleus (large arrow) and the golgi apparatus and mitochondria (small arrows) in E. (B, D, and F) 3 MBq 90Y/ml. Arrows demonstrate damaged cells in B and D. In F remnants of organelles of a dead cell are visible. (A–D) bar=27 µm, (E, F) bar=0.2 µm.

Figure 2 .

Figure 2

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[3H]Proline incorporation in chondrocyte alginate cultures and cartilage explants two weeks after a four day period of 90Y irradiation. The bars show the dose dependent decrease of [3H]proline incorporation (p<0.004 by one way ANOVA) related to non-irradiated control cultures. Mean values (SD); n=6 (explants n=3); *p<0.05 v control by two tailed Student's t test.

Figure 3 .

Figure 3

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Immunocytochemical staining of collagen type II on cultures of chondrocytes in alginate beads two weeks after a four day period of 90Y irradiation. The figure shows the dose dependent decrease of collagen type II expression (brown staining; arrows demonstrate cells) compared with (A) the non-irradiated control; (B) 0.375 MBq; (C) 1 MBq 90Y. Bar=15.38 µm

Figure 4 .

Figure 4

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NO accumulation in supernatants of seven day old chondrocyte alginate and explant cultures, human synovial fluid (synovia) samples, and cell-free culture medium during four days of 90Y irradiation. The bars show the dose dependent increase of NO accumulation in the different systems. Mean values (SD); n=6 (explants n=3); *p<0.001 v control by two tailed Student's t test; p<0.001 by one way ANOVA.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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