title: Secreted klotho protein attenuates osteogenic differentiation of human bone marrow mesenchymal stem cells in vitro via inactivation of the FGFR1/ERK signaling pathway.
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.
authors.affiliation: a Department of Orthopedics , Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: a Department of Orthopedics , Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , People's Republic of China.
authors.forename: Deting
authors.initials: D
authors.lastname: Xue
authors.affiliation: a Department of Orthopedics , Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , People's Republic of China.
authors.forename: Dongcai
authors.initials: D
authors.lastname: Hu
authors.affiliation: a Department of Orthopedics , Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xie
authors.affiliation: a Department of Orthopedics , Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , People's Republic of China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Tao
authors.affiliation: a Department of Orthopedics , Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhu
authors.affiliation: a Department of Orthopedics , Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , People's Republic of China.
authors.forename: Erman
authors.initials: E
authors.lastname: Chen
authors.affiliation: a Department of Orthopedics , Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , People's Republic of China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Pan
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002113:Calcification, Physiologic / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D000090265:Klotho Proteins; D020935:MAP Kinase Signaling System / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D005419:Flavonoids; C115711:PD 173074; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C493709:RUNX2 protein, human; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D048049:Extracellular Signal-Regulated MAP Kinases; D000469:Alkaline Phosphatase; D005966:Glucuronidase; D000090265:Klotho Proteins; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Klotho; differentiation; mesenchymal stem cells; osteogenic