Switching of Mesenchymal Progenitor Cell (MPC) Differentiation from Chondrogenesis to Osteogenesis

• Main Authors: Wen-Ho Cheng, 鄭溫河
• Other Authors: Yu-Hui Tsai
• Format: Others
• Language: en_US
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/91666796564583111513

碩士 === 臺北醫學大學 === 細胞及分子生物研究所 === 92 === Mesenchymal progenitor cells (MPCs) are multipotential cells which can differentiate into many types of cells. In animal embryonic skeleton development, cartilage develops first, and bone formation follows. Whether the bone formation is derived directly from MPCs or chondrocytes is still unclear. According to previous study, MPCs differentiate into chondrocyte-like cells in the presence of dexamethasone (DEX) and transforming growth factor-β1 (TGF-β1). However, if MPCs are on the way to chondrogenic lineage, could they be re-directed to osteogenesis. In this study, it was intended to use MPCs in the chondrogenic pathway as a model to investigate whether the changes in microenvironment will switch MPC differentiation from chondrogenesis to osteogenesis. This experimental model may reveal whether MPCs in Chondrogenic pathway are limited in differentiating potential or retain ability to differentiate into other lineages. In our experimental model, mesenchymal progenitor cells (MPCs) pre-treated with dexamethasone and TGF-β1 for 7 days, to induce chondrogenic differentiation, and then treated with osteogenic growth factor or osteogenic medium for another 7 days. It was found that the activity of alkaline phosphatase (ALP), the osteogenic marker, of treated MPCs was greatly up-regulated for 3 to 6 folds. Meanwhile, the expression of type II collagen, the important marker for chondrogenesis of MPCs, was found in cells treated only with DEX/ TGF-β1 but not cells treated with osteogenic factor or control group. On the other hand, the expression of another important osteogenic marker core-bonding factor a1 (Cbfa1) was also shown in MPCs on the way to chondrogenesis and then treated with osteogenic growth factors and osteogenic medium. Furthermore, chondrocytes treated with osteogenic growth factors and osteogenic medium for 2 weeks also expressed higher type I collagen and lower type II collagen than the control cells. According to the above results, it appears that after MPCs have been induced to initiate chondrogenic differentiation, their differentiation fate might continue toward chondrogenesis, or be switched to osteogenic differentiation depending on the factors presented in their microenvironment. Furthermore, in the presence of these osteogenic growth factor or medium, chondrocytes might also be induced to differentiate towards osteogenic pathway.