Inhibition of focal adhesion turnover prevents osteoblastic differentiation through β-catenin mediated transduction of pro-osteogenic substrate.

ABSTRACT: The mechanism by which substrate surface characteristics are transduced by osteoblastic cells and their progenitors is not fully known. Data from previous studies by our group suggest the involvement of β-catenin in the mechanism by which substrate surface characteristics are transduced. This focal adhesion and β-catenin mediated mechanism functions through the liberation of β-catenin from focal adhesion complexes in response to pro-osteogenic substrate (POS) characteristics. After liberation, β-catenin translocates and facilitates upregulation of genes associated with osteogenesis. It is not known whether the observed correlation between focal adhesion turnover and β-catenin translocation directly results from focal adhesion turnover. In this study we inhibited focal adhesion turnover using a focal adhesion kinase inhibitor PF-573228. We found that inhibition of focal adhesion turnover resulted in an abrogation of the more rapid translocation and increased transcriptional activity of β-catenin induced by POS. In addition, inhibition of focal adhesion turnover mitigated the increase in osteoblastic differentiation induced by a POS as measured by alkaline phosphatase enzymatic activity and osteogenic gene and protein expression. Together, these data, coupled with previous findings, suggest that the observed β-catenin translocation is a result of focal adhesion turnover, providing evidence for a focal adhesion initiated, β-catenin mediated mechanism of substrate surface signal transduction.

SUBMITTER: Juhl OJ 

PROVIDER: S-EPMC9306686 | biostudies-literature |

REPOSITORIES: biostudies-literature