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. 2004 Mar;63(3):240–244. doi: 10.1136/ard.2002.003749

Tenascin and aggrecan expression by articular chondrocytes is influenced by interleukin 1ß: a possible explanation for the changes in matrix synthesis during osteoarthritis

D Pfander 1, N Heinz 1, P Rothe 1, H Carl 1, B Swoboda 1
PMCID: PMC1754923  PMID: 14962956

Abstract

Objective: To analyse the distribution patterns of tenascin and proteoglycans in normal and osteoarthritic cartilage, and to determine the effect of interleukin 1ß (IL1ß) on aggrecan and tenascin expression by human articular chondrocytes in vitro.

Methods: Normal and osteoarthritic cartilage and bone samples were obtained during total knee replacements or necropsies. After fixation and decalcification, paraffin embedded specimens were sectioned perpendicular to the surface. Specimens were graded according to Mankin and subdivided into those with normal, and mild, moderate, and severe osteoarthritic lesions. Serial sections were immunostained for tenascin. Tenascin expression by healthy and osteoarthritic chondrocytes was quantified by real time polymerase chain reaction (PCR). Furthermore, in cell culture experiments, human articular chondrocytes were treated with 0.1 or 10 ng/ml IL1ß. Real time PCR analyses of aggrecan and tenascin transcripts (normalised 18S rRNA) were conducted to determine the effect of IL1ß on later mRNA levels.

Results: Tenascin was immunodetected in normal and osteoarthritic cartilage. In osteoarthritic cartilage increased tenascin staining was found. Tenascin was found specifically in upper OA cartilage showing a strong reduction of proteoglycans. Greatly increased tenascin transcript levels were detected in osteoarthritic cartilage compared with healthy articular cartilage. IL1ß treatment of articular chondrocytes in vitro significantly increased tenascin transcripts (~200% of control) and strongly reduced aggrecan mRNA levels (~42% of control).

Conclusions: During progression of osteoarthritis the switch in matrix synthesis occurs mainly in upper osteoarthritic cartilage. Furthermore, changes in synthesis patterns of osteoarthritic chondrocytes may be significantly influenced by IL1ß, probably diffusing from the joint cavity within the upper osteoarthritic cartilage.

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Figure 1 .

Figure 1

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Serial sections of normal and OA cartilage. The tenascin deposition in healthy cartilage varied interindividually. Normal cartilage stained for proteoglycans (A) and immunostained for tenascin (B) shows pericellular/territorial tenascin deposition around the superficial and upper middle zone chondrocytes (weak immunostaining). (C) Mild OA lesion with decreased proteoglycan staining of the upper cartilage (safranin O staining). (D) Immunohistochemical analysis of tenascin in the same section as shown in C (note the territorial staining around the middle zone chondrocytes indicated by arrows). (E) Severe OA cartilage lesion showing a strong reduction of proteoglycans, deep clefts within the deep zone, and chondrocyte clusters in all zones (safranin O staining). (F) Immunostaining of tenascin in the same section as shown in E (note the strong tenascin staining in cartilage areas showing the absence of proteoglycans indicated by arrows). The bar in A represents 100 µm in A-F.

Figure 2 .

Figure 2

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Bars represent the several-fold changes of tenascin mRNA levels (normalised to 18S rRNA) in mild and severe OA lesions compared with healthy cartilage samples (one fold expression). Bars are means (SD). *p<0.05 versus healthy samples.

Figure 3 .

Figure 3

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Bars represent the several-fold changes of aggrecan mRNA levels (normalised to 18S rRNA) of IL1ß treated chondrocytes compared with untreated control chondrocytes (one fold expression). Articular chondrocytes were cultured under serum free conditions for 18 hours in the absence or presence of 0.1 and 10 ng/ml IL1ß, respectively. Results are from four independent cell culture experiments. Bars represent means (SD). **p<0.01 versus control.

Figure 4 .

Figure 4

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Bars represent the several-fold changes of tenascin mRNA levels (normalised to 18S rRNA) of IL1ß treated chondrocytes compared with untreated control chondrocytes (one fold expression). Articular chondrocytes were cultured under serum free conditions for 18 hours in the absence or presence of 0.1 and 10 ng/ml IL1ß, respectively. Results are from four independent experiments. Bars represent means (SD). **p<0.01 versus control.

Selected References

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

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