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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2000 Jun;59(6):448–454. doi: 10.1136/ard.59.6.448

Expression of thrombospondin-1 and its receptor CD36 in human osteoarthritic cartilage

D Pfander 1, T Cramer 1, D Deuerling 1, G Weseloh 1, B Swoboda 1
PMCID: PMC1753153  PMID: 10834862

Abstract

OBJECTIVE—Thrombospondin-1 (TSP-1), a trimeric glycoprotein, is involved in cell-matrix interactions of various tissues, particularly in cartilage. Biochemical analyses show expression of TSP-1 in human cartilage, but its cellular source as well as the presence of its main surface receptors CD36 and CD51 in normal and osteoarthritic cartilage remain unknown. Therefore, to localise TSP-1 and its receptors immunohistochemistry and in situ hybridisation were used.
METHODS—Radioactive in situ hybridisations with an RNA probe that encodes TSP-1 combined with immunostaining were carried out to investigate the expression patterns of TSP-1, CD36, and CD51 in seven normal and 23 osteoarthritic human cartilage samples.
RESULTS—In normal cartilage TSP-1 was present mainly in the middle and upper deep zone. RNA expression was predominantly seen over chondrocytes of the middle zone. CD36 was found in chondrocytes of the superficial and upper middle zone. In mild and moderate osteoarthritic cartilage an increased number of TSP-1 expressing chondrocytes were seen and an increased pericellular staining close to the surface. In severe osteoarthritic cartilage a decrease in the number of TSP-1 synthesising chondrocytes and a strong reduction in matrix staining were observed. Most of these severe osteoarthritic samples showed a strongly enhanced number of CD36 positive chondrocytes.
CONCLUSION—The cellular source of TSP-1 in normal cartilage is mainly mid-zone chondrocytes, which also express CD36. In early osteoarthritic cartilage lesions an increase of TSP-1 was seen, whereas reduced TSP-1 synthesis is paralleled by a strong decrease in TSP-1 protein staining in severe osteoarthritis. Furthermore, in severe osteoarthritic cartilage the number of CD36 immunostained chondrocytes is significantly increased.



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Figure 1  .

Figure 1  

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(A) Normal cartilage (three of seven samples, Mankin 1 and 0). Immunohistochemical staining of TSP-1 in normal human cartilage without TSP-1 staining in the superficial zone (S indicates cartilage surface). (B) In situ hybridisation of TSP-1 shows strong expression mainly in middle zone chondrocytes (open arrowheads). (C) High power magnification of typical zonal areas of the superficial (S), middle (M) and the deep (D) zone with positive TSP-1 RNA signals over chondrocytes of the superficial and middle zones (closed arrowheads). (D) Typical distribution of CD36 immunostained chondrocytes in normal cartilage. Bar represents 115 µm in figs A, B, and D and 30 µm in fig C. 

Figure 2  .

Figure 2  

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(A) Mild OA cartilage (one of seven samples, Mankin 4). Immunohistochemical staining of TSP-1 in mild OA cartilage showing chondrocytes with pericellular TSP-1 staining in the upper middle zone (closed arrowheads) and a predominantly interterritorial staining in the deep zone (s indicates cartilage surface). (B) In situ hybridisation of TSP-1 shows expression of middle and deep zone chondrocytes (open arrowheads). (C) CD36 positive chondrocytes are present in the middle and upper deep zones. Bar represents 125 µm in figs A, B, and C. 

Figure 3  .

Figure 3  

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(A) Moderate OA cartilage (one of seven samples, Mankin 7). TSP-1 protein in moderate OA cartilage is present in the upper regions with a pericellular distribution, whereas in the deeper regions a slight interterritorial staining persists (s indicates cartilage surface). (B) Strong TSP-1 expression of the pericellularly stained chondrocytes was found by in situ hybridisation. (C) CD36 positive chondrocytes in co-localisation with TSP-1 expressing chondrocytes. Bar represents 125 µm in figs A, B, and C. 

Figure 4  .

Figure 4  

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(A) Severe OA cartilage (two of nine samples, Mankin 13 and 14). Weak TSP-1 staining in the pericellular matrix of clustered chondrocytes (closed arrowhead) and a weak staining territorial and interterritorial on the right side (area between open arrowheads). (B) Magnification of a large chondrocyte cluster with a pericellular TSP-1 staining (closed arrowheads). (C) Adjacent slide with clustered chondrocytes showing TSP-1 expression (closed arrowheads). (D) Strong CD-36 protein expression of nearly 90% of the remaining clustered chondrocytes (closed arrowheads). Bar represents 125 µm in figs A and D, and 50 µm in B and C. 

Figure 5  .

Figure 5  

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(A) Osteophytes. Strong immunohistochemical TSP-1 staining in osteophytes (s indicates cartilage surface). (B) Paralleled by a strong TSP-1 expression by in situ hybridisation (area between closed arrowheads). (C) Most of the chondrocytes are CD36 positive. Bar represents 125 µm in figs A, B, and C. 

Selected References

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

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