Secreted klotho protein attenuates osteogenic differentiation of human bone marrow mesenchymal stem cells in vitro via inactivation of the FGFR1/ERK signaling pathway.

Increasing evidence indicates that the osteogenic differentiation of mesenchymal stem cells (MSCs) is related to bone formation, heterotopic ossification, and even vascular calcification. Therefore, it is essential to understand the microenvironment that regulates these processes. The Klotho gene plays an important role in tissue mineralization, and its secreted protein functions as a hormone. We investigated the effects of secreted Klotho protein on the osteogenesis of human bone marrow MSC (hBMSCs). To this end, the cells received osteogenic medium with or without Klotho protein. The results showed that osteoblast-specific gene expression and mineral deposition were decreased when MSCs were incubated with Klotho. Klotho reduced the expression of fibroblast growth factor receptor 1 (FGFR1) and phosphorylated extracellular signal-regulated kinase 1/2. However, both MEK and FGFR1 inhibitors delayed bone mineral formation more than Klotho. These data suggest that secreted Klotho protein attenuates the osteogenic differentiation of hBMSCs in vitro through FGFR1/ERK signaling.