FGF23 affects the lineage fate determination of mesenchymal stem cells.
FGF23 is a bone-derived hormone that regulates mineral metabolism by inhibiting renal tubular phosphate reabsorption and suppressing circulating 1,25(OH)2D and PTH levels. These effects are mediated by FGF-receptor binding and activation in the presence of its coreceptor Klotho, which is expressed in the distal tubules of the kidney. Recently, expression of Klotho in skeletal tissues has been reported, indicating a direct, yet unclear, extrarenal effect of FGF23 on cells involved with bone development and remodeling. In the present study, we found that bone marrow stromal cells harvested from Klotho null mice developed fewer osteoblastic but more adipocytic colonies than cells from wild-type mice. The underlying mechanism was explored by experiments on mouse C3H10T1/2 cells. We found that Klotho was weakly expressed and that FGF23 dose-dependently affected the lineage fate determination. The effects of FGF23 on cell differentiation can be diminished by SU 5402, a specific tyrosine kinase inhibitor for FGF receptors. Our results indicate that FGF23 directly affects the differentiation of bone marrow stromal cells.
Division of Orthopedics and Biotechnology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Huddinge, 14186, Stockholm, Sweden.
Yan
Y
Li
Xu
X
He
Hannes
H
Olauson
Tobias E
TE
Larsson
Urban
U
Lindgren
D017667:Adipocytes / Q000166:cytology; D000375:Aging; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D000090265:Klotho Proteins; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008809:Mice, Inbred C3H; D010006:Osteoblasts / Q000378:metabolism; D010024:Osteoporosis / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism
C000717428:Fgf23 protein, mouse; D010710:Phosphates; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins