The effect of PAPP-A on the proliferation and differentiation of MG-63 and human adult mesenchymal stem cells.

摘要

Pregnancy associated plasma protein-A (PAPP-A) plays an important role in the activity of the Insulin-like Growth Factor (IGF) family by proteolytically cleaving IGF-Binding Protein-4 (IGFBP-4) causing it to dissociate from IGF-I in vivo. This increases the bioavailability of IGF-I, allowing IGF-I to participate in growth and development. My goal was to evaluate the ability of PAPP-A to directly stimulate proliferation and differentiation of human adult mesenchymal stem cells (hAMSC) cells in vitro.;To test for differentiation, hAMSC were treated with mesenchymal stem cell growth medium---MSCGM (negative control), an osteogenic supplement (positive control) or 200 ng/mL PAPP-A in MSCGM for multiple time points. hAMSC were harvested for RNA extraction followed by qPCR analysis to detect osteoblastic differentiation via multiple marker genes. qPCR results showed a statistically significant increase in Runx2 and alkaline phosphatase gene expression in hAMSC when treated with PAPP-A for 12 and 18 hours respectively.;My results indicate that addition of PAPP-A to cell culture medium does not affect proliferation of hAMSC. However, treatment with PAPP-A for 12 and 18 hours increases Runx2 and alkaline phosphatase gene expression respectively in hAMSC suggesting that PAPP-A plays a role in osteoblast differentiation in an in vitro environment. Further elucidation of this role is necessary to determine PAPP-A's involvement in osteoblast development and its potential therapeutic role in bone degenerative diseases such as osteoporosis. (Abstract shortened by UMI.).