Soluble Klotho regulates bone differentiation by upregulating expression of the transcription factor EGR-1

被引：17
作者：
Nguyen Khanh Toan [1 ]
Nguyen Chi Tai [1 ]
Kim, Soo-A [2 ]
Ahn, Sang-Gun [1 ]
机构：
[1] Chosun Univ, Sch Dent, Dept Pathol, 309 Pimun Daero, Gwangju 61452, South Korea
[2] Dongguk Univ, Sch Oriental Med, Dept Biochem, Gyeongju, South Korea
来源：
FEBS LETTERS | 2020年 / 594卷 / 02期
基金：
新加坡国家研究基金会;
关键词：
EGR-1; osteogenic differentiation; soluble Klotho; KIDNEY; OSTEOBLAST; PROTECTS; FIBROSIS; SUPPORTS; TARGET; MATRIX; FGF23; MICE;
D O I：
10.1002/1873-3468.13613
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：290 / 300
页数：11
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