Pfander D, Cramer T, Deuerling D, Weseloh G, Swoboda B
Department of Orthopaedic Surgery, University of Erlangen-Nuernberg, Germany.
Ann Rheum Dis. 2000 Jun;59(6):448-54. doi: 10.1136/ard.59.6.448.
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.
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.
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.
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.
血小板反应蛋白-1(TSP-1)是一种三聚体糖蛋白,参与多种组织的细胞与基质相互作用,尤其是在软骨中。生化分析显示TSP-1在人软骨中有表达,但其细胞来源以及在正常和骨关节炎软骨中其主要表面受体CD36和CD51的存在情况仍不清楚。因此,采用免疫组织化学和原位杂交技术来定位TSP-1及其受体。
使用编码TSP-1的RNA探针进行放射性原位杂交并结合免疫染色,以研究7个正常和23个骨关节炎人软骨样本中TSP-1、CD36和CD51的表达模式。
在正常软骨中,TSP-1主要存在于中层和深层上部区域。RNA表达主要见于中层区域的软骨细胞。CD36在表层和中层上部的软骨细胞中被发现。在轻度和中度骨关节炎软骨中,可见表达TSP-1的软骨细胞数量增加,且靠近表面的细胞周围染色增强。在重度骨关节炎软骨中,观察到合成TSP-1的软骨细胞数量减少,基质染色强烈减少。这些重度骨关节炎样本中的大多数显示CD36阳性软骨细胞数量显著增加。
正常软骨中TSP-1的细胞来源主要是中层软骨细胞,其也表达CD36。在早期骨关节炎软骨病变中可见TSP-1增加,而在重度骨关节炎中TSP-1合成减少与TSP-1蛋白染色强烈减少平行。此外,在重度骨关节炎软骨中,CD36免疫染色的软骨细胞数量显著增加。