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

页码：290 / 300

页数：11

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