激活的wntβ-catenin信号经p53降低关节软骨间充质祖细胞增殖及分化能力的研究-study on activated wnt β - catenin signal decreasing proliferation and differentiation ability of articular cartilage mesenchymal progenitor cells through p53.docx

第三军医大学硕士学位论文 第三军医大学硕士学位论文 PAGE PAGE 3 ActivatedWnt3a/beta-catenin signalinhibits proliferation and chondrocyte differentiation of articular cartilage mesenchymal progenitor cells through p53pathway Abstract Background Currently, the number of primary osteoarthritis (Osteoarthritis, OA) is growingup to become to the second leading cause of disability in the elderly, but its pathogenesis is not clear. Recent studies have shown that: the aging of the stem cell tissue and organ aging could be the important internal factors. In 2004, Dowthwaite GP found that human articular cartilage existin mesenchymal progenitor cells (MPCs).On the other hand, Alsalameh havefound the number of MPCs in normal articular cartilage is more than primary OA articular cartilage. Our previous study also implies that: the number of MPCs in OA articular cartilage per unitissignificantly less than the normal group, and their proliferation and differentiate to chondrocytes is also significantly lowerthan the normal group. We may infer that the MPCs in articular cartilage play an important role in the repair of cartilage damage, thus, the MPCs aging have a particular relation to degeneration of articular cartilage in OA,Unfortunatelythe research of mechanism of MPCs aging in articular cartilages on going and not clear yet. Recently data have shownthat OA articular cartilage exist the expression of Wnt proteins. In mechanical injury of articular cartilage, expression of Wnt signal target genes Axin-2 and c-JUN raised, and secreted frizzled protein is downerregulated, it suggests that Wnt signal is active. Another recent study found that there is a relationship between the Wnt signal pathway and p53/p21 pathway. Target genes of the Wnt signal pathway is TCF4, which is also the target gene of p53. Over expression of β-catenin in retinoblastoma cell cytoplasm can increase the transcriptional activity of p53. In the present study, a clear increase in p53 and p21 expression was observed in the ORS(ol