EXPRESSION OF THROMBOSPONDIN-1 AND ITS RECEPTOR CD36 IN HUMAN ARTICULAR CARTILAGE

Abstract

Objective

Thrombospondin-1 (TSP-1) a trimeric heigh-molecular weight glycoprotein is a multifunctional extra-cellular matrix protein. TSP-1 is involved in cell-matrix interactions of a various tissues. TSP-1 can bind to cells via different TSP-1 domains, its main receptors are CD 36 and CD51 (a_vb₃-integrin). Nothern and western analysis showed the expression of TSP-1 in human cartilage, but its cellular source as well as the presence of its receptors CD36 and CD51 in normal and osteoarthritic cartilage are totally unknown.

Materials

We investigated 7 normal and 23 osteoarthritic cartilage samples on the expression patterns of TSP-1, CD36 and CD51, by immunohistochemistry and in situ hybridization.

Results

In normal cartilage we found TSP-1 to be present in the middle and upper deep zone. Predominantly chondrocytes of the middle zone showed RNA-expression. Also, its receptor CD36 was found mainely in the chondrocytes of the superficial and middle zone. In moderate osteoarthritic cartilage we found an increased number of TSP-1 expressing chondrocytes, as well as an increased pericellular immunostainig quite near to the surface. However, a small number of CD36 positive cells were observed across the whole OA cartilage. In severe osteo-arthritic cartilage were observed a strong decrease in TSP-1 synthesizing chondrocytes by in situ hybridization as well as a strong reduction in the immunohistochemically matrix staining. In contrast to the decrease in TSP-1 we observed in 5 out of 8 these samples a overall enhanced number in CD 36 stained chondrocytes. Further, osteophytes with strong TSP-1 expression showed a large number of CD36 positive cells. However, CD51 positive chondrocytes could not be detected.

Conclusion

TSP-1 and its receptor are expressed in normal and osteoarthritic cartilage. The source of TSP-1 in normal cartilage are the middle zone chondrocytes, which also express the CD36-receptor. In early osteoarthritic cartilage an increase of TSP-1 was observed, whereas in later osteoarthritic cartilage TSP-1-synthesis is strongly decreased. It can be hypothesized that the strong enhanced number of CD36-stained chondrocytes in severe OA cartilage is a sign of chondrocytes frustrate efforts to contact the ECM, by binding to TSP-1.