ELAV-like RNA binding protein 1 regulates osteogenesis in diabetic osteoporosis: Involvement of divalent metal transporter 1

• Published in: Molecular and cellular endocrinology Vol. 546; p. 111559
• Main Authors: Ren, Yuanfei, Yang, Maowei, Wang, Xindong, Xu, Buxuan, Xu, Zerong, Su, Bo
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 15.04.2022
• Subjects: Animals; Diabetes Mellitus - genetics; Diabetic osteoporosis; Divalent metal transporter 1; ELAV-Like Protein 1; ELAV-Like RNA binding Protein 1; Iron; Iron overload; MC3T3-E1 cells; Mice; Osteoblast differentiation; Osteogenesis - genetics; Osteoporosis - metabolism; RNA-Binding Proteins; Iron overload; ELAV-Like RNA binding Protein 1; Divalent metal transporter 1; MC3T3-E1 cells; Diabetic osteoporosis; Osteoblast differentiation
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2022.111559

Diabetic osteoporosis (DOP) is a complication of diabetes mellitus (DM) and occurs due to alterations in bone metabolism under hyperglycemic condition. ELAV-like RNA binding protein 1 (ELAVL1) is abnormally up-regulated in diabetes-related diseases. Bioinformatics prediction indicates that divalent metal transporter 1 (DMT1) is a potential target of ELAVL1. To explore the role of ELAVL1 and the involvement of ELAVL1/DMT1 axis in DOP, we established a mouse model of DM by administration of high-fat diet and intraperitoneal injection with streptozotocin (STZ). The expression of ELAVL1 and DMT1 was increased in the bone tissues of DM mice. Knockdown of ELAVL1 reduced iron level and oxidative stress, promoted osteogensis, and prevented bone mass loss, thus mitigating DOP in DM mice. In vitro, mouse pre-osteoblast MC3T3-E1 cells were treated with high glucose (25 mM) and ferric ammonium citrate (FAC, 200 μM). The inhibitory effects of ELAVL1 knockdown on iron accumulation and oxidative stress were evidenced in MC3T3-E1 cells. Knockdown of ELAVL1 enhanced osteoblast viability, differentiation and mineralization. Notably, the expression of DMT1 was positively correlated with that of ELAVL1 in vivo and in vitro. Overexpression of DMT1 abolished the effect of ELAVL1 knockdown on the behaviors of MC3T3-E1 cells, suggesting that ELAVL1 might function through regulating DMT1. In conclusion, knockdown of ELAVL1 likely alleviated DOP by inhibiting iron overload and oxidative stress and promoting osteogenesis, and DMT1 might be involved in this process. These findings provide insights into the pathogenesis of DOP and suggest a potential therapeutic target for DOP treatment. •The expression of ELAVL1 and DMT1 was increased in bone tissues of DM mice.•Kncokdown of ELAVL1 inhibited iron overload and oxidative stress in bone tissues of DM mice.•Knockdown of ELAVL1 promoted osteogenesis and prevented bone mass loss in DM mice.•The expression of DMT1 was positively correlated with that of ELAVL1.•ELAVL1 functioned by targeting DMT1 in high glucose-treated MC3T3-E1 cells.