Analysis of gene expression in chondrocytes using DNA microarrays (DNA chips)

1)应用基因芯片技术分析了软骨细胞前细胞系ATDC5的基因表达。2)用基因芯片技术分析类风湿性关节炎(RA)和骨性关节炎(OA)来源滑膜细胞的基因表达。在OA中STAT、PKC、caspase和IGFBP表达上调，CDC25、Rho和Fgf7在RA中表达上调。C-fos和c-jun在RA中的表达也上调。3)应用DNA微阵列技术分析了软骨肉瘤软骨细胞系HCS-2/8的基因表达，发现CTGF可上调多种MAP蛋白的表达。我们发现CTGF通过ERK促进HCS-2/8细胞的增殖，并通过p38MAPK促进HCS-2/8细胞的分化。4)将X型胶原启动子控制下表达CTGF的表达载体注射到受精卵中，获得CTGF过表达的转基因小鼠。外源性CTGF在转基因小鼠的软骨组织中有表达，而在转基因小鼠的软骨组织中内源性表达减少。转基因小鼠具有骨密度降低的侏儒症表型。

1) Gene expression in a pre-chondrocytic cell line ATDC5 was analyzed by using DNA microarrays. Several genes showed significant difference of expression level between undifferentiated and differentiated stage of ATDC5 cells.2) Gene expression in RA (rheumatoid arthritis)- or OA (osteoarthritis)-derived synoviocytes was analyzed by using DNA microarrays. The expression of STAT, PKC, caspase and IGFBP was upregulated in OA, and the expression of CDC25, RHO and FGF7 was up-regulated in RA. The expression of c-fos and c-jun was also up-regulated in RA. Immunostaining showed that apoptosisrelated caspase-9 was highly expressed in OA-derived synoviocytes and cartilage tissues.3) Gene expression in a chondrosarcoma-derived chondrocytic cell line, HCS-2/8 was analyzed by using DNA microarrays.The expression of several MAP kinases was up-regulated by the addition of CTGF. We found that CTGF stimulated the proliferation of HCS-2/8 cells through Erk, and the differentiation of HCS-2/8 cells through p38 MAPK.4) CTGF-overexpressed transgenic mice were prepared by injection of expression vectors in which CTGF was expressed under the control of type XI collagen promoter into fertilized eggs. The expression of exogenous CTGF was observed in the cartilage tissues of transgenic mice, but its endogenous expression was decreased in transgenic mice. It was also showed that transgenic mice had the phenotype of dwarfism with decreased bone density.