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Soluble Klotho regulates bone differentiation by upregulating expression of the transcription factor EGR‐1
Author(s) -
Toan Nguyen Khanh,
Tai Nguyen Chi,
Kim SooA,
Ahn SangGun
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13613
Subject(s) - runx2 , osteoblast , klotho , osteocalcin , transcription factor , zinc finger transcription factor , bone morphogenetic protein 2 , microbiology and biotechnology , chemistry , ascorbic acid , zinc finger , biology , alkaline phosphatase , endocrinology , biochemistry , gene , enzyme , food science , in vitro , kidney
Klotho is a transmembrane protein known to regulate aging and lifespan. Soluble Klotho (sKL), a truncated form of Klotho, regulates various cell signaling pathways, including bone development. Here, we investigated the relationship between sKL and the zinc finger transcription factor early growth response protein 1 (EGR‐1) on bone formation. We find that sKL induces the expression of EGR‐1 mRNA and protein. Through mutational analysis, we identify the 130 bp region on the EGR‐1 promoter that is responsive to sKL overexpression. Additionally, sKL induces the expression of markers of bone differentiation (BMP2, RUNX2, ALP, COL1A, and osteocalcin) in osteoblast MC3T3 cells. EGR‐1 siRNA decreases the bone mineralization induced by sKL or ascorbic acid/glycerol 2‐phosphate in MC3T3 cells. Our results suggest that sKL may regulate bone development through EGR‐1 expression.