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

Wei Zhang; Deting Xue; Dongcai Hu; Tao Xie; Yiqing Tao; Ting Zhu; Erman Chen; Zhijun Pan

doi:10.3109/08977194.2015.1108313

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

Growth Factors. 2015;33(5-6):356-65. doi: 10.3109/08977194.2015.1108313. Epub 2015 Nov 25.

Authors

Wei Zhang¹, Deting Xue¹, Dongcai Hu¹, Tao Xie¹, Yiqing Tao¹, Ting Zhu¹, Erman Chen¹, Zhijun Pan¹

Affiliation

¹ a Department of Orthopedics , Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , People's Republic of China.

PMID: 26607681
DOI: 10.3109/08977194.2015.1108313

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.

Keywords: Klotho; differentiation; mesenchymal stem cells; osteogenic.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkaline Phosphatase / metabolism
Bone Marrow Cells / cytology
Calcification, Physiologic / genetics
Calcification, Physiologic / physiology
Cell Differentiation / physiology*
Cells, Cultured
Core Binding Factor Alpha 1 Subunit / biosynthesis
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
Extracellular Signal-Regulated MAP Kinases / metabolism*
Flavonoids / pharmacology
Glucuronidase / metabolism*
Humans
Klotho Proteins
MAP Kinase Signaling System / physiology*
Mesenchymal Stem Cells / cytology*
Osteogenesis / genetics
Osteogenesis / physiology*
Protein Kinase Inhibitors / pharmacology
Pyrimidines / pharmacology
Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
Receptor, Fibroblast Growth Factor, Type 1 / antagonists & inhibitors
Receptor, Fibroblast Growth Factor, Type 1 / metabolism*

Substances

Core Binding Factor Alpha 1 Subunit
Flavonoids
PD 173074
Protein Kinase Inhibitors
Pyrimidines
RUNX2 protein, human
FGFR1 protein, human
Receptor Protein-Tyrosine Kinases
Receptor, Fibroblast Growth Factor, Type 1
Extracellular Signal-Regulated MAP Kinases
Alkaline Phosphatase
Glucuronidase
Klotho Proteins
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one