m6A demethylase FTO and osteoporosis: potential therapeutic interventions

Mei Huang; Jianmin Guo; Lifei Liu; Haiming Jin; Xi Chen; Jun Zou

doi:10.3389/fcell.2023.1275475

m6A demethylase FTO and osteoporosis: potential therapeutic interventions

Front Cell Dev Biol. 2023 Nov 10:11:1275475. doi: 10.3389/fcell.2023.1275475. eCollection 2023.

Authors

Mei Huang¹, Jianmin Guo¹, Lifei Liu^{1

2}, Haiming Jin³, Xi Chen⁴, Jun Zou¹

Affiliations

¹ School of Kinesiology, Shanghai University of Sport, Shanghai, China.
² Department of Rehabilitation, The People's Hospital of Liaoning Province, Shenyang, China.
³ Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
⁴ School of Sports Science, Wenzhou Medical University, Wenzhou, China.

Abstract

Osteoporosis is a common bone disease, characterized by a descent in bone mass due to the dysregulation of bone homeostasis. Although different studies have identified an association between osteoporosis and epigenetic alterations in osteogenic genes, the mechanisms of osteoporosis remain unclear. N6-methyladenosine (m6A) modification is a methylated adenosine nucleotide, which regulates the translocation, exporting, translation, and decay of RNA. FTO is the first identified m6A demethylase, which eliminates m6A modifications from RNAs. Variation in FTO disturbs m6A methylation in RNAs to regulate cell proliferation, differentiation, and apoptosis. Besides, FTO as an obesity-associated gene, also affects osteogenesis by regulating adipogenesis. Pharmacological inhibition of FTO markedly altered bone mass, bone mineral density and the distribution of adipose tissue. Small molecules which modulate FTO function are potentially novel remedies to the treatment of osteoporosis by adjusting the m6A levels. This article reviews the roles of m6A demethylase FTO in regulating bone metabolism and osteoporosis.

Keywords: FTO; FTO inhibitor; bone metabolism; m6A methylation; osteoporosis.

Publication types

Review

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. The work is supported by the funding from Foundation of Zhejiang Educational Committee (Grant No. Y202146899), the National Natural Science Foundation of China (Grant No. 81702235), Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, and Shanghai Key Lab of Human Performance (Shanghai University of sport) (Grant No. 11DZ2261100).