Tissue inhibitor of metalloproteinase-1 (TIMP-1) regulates mesenchymal stem cells through let-7f microRNA and Wnt/β-catenin signaling

摘要

Human mesenchymal stem cells (hMSCs) originate primarily from bone marrow and are multipotent, meaning they can differentiate into various cell types, including bone cells (osteocytes), cartilage cells (chondrocytes), and fat cells (adipocytes), in response to stimulation by various environmental factors (1). As a source of adult stem cells for transplantation from the same patient (autologous), hMSCs have great promise in regenerative therapies (2). However, the molecular mechanisms that govern hMSC differentiation remain unclear. Investigating one of the complex signaling pathways involved, we found that a molecule called TIMP-1 inhibits growth and differentiation of these stem cells. We found that it operates by affecting the Wnt/p-catenin signaling pathway before and after genes have produced proteins (posttranscriptionally and posttransla-tionally, respectively).