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Research Paper

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

, , , , , , & show all
Pages 356-365 | Received 20 Sep 2015, Accepted 12 Oct 2015, Published online: 25 Nov 2015
 

Abstract

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.

Acknowledgement

None.

Declaration of interest

All authors have contributed significantly and are in agreement with the content of the manuscript. All authors have no relevant financial relationships to disclose. This work was supported by a grant from the National Natural Science Foundation of China (No. 81271973 and No. 81201397), the Zhejiang Provincial Natural Science Foundation of China (No. LY15H060001; No. LY15H060002 and No. LY13H060002), and Zhejiang Medical and Health Science and Technology Plan Project (No. 2015116473).

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