FTO in Bone Diseases: Functions, Mechanisms and Therapeutic Potential

Area of Science:

• Skeletal biology and epigenetics
• RNA modification and cellular regulation

Background:

• Skeletal homeostasis involves complex cell interactions, and its disruption leads to diseases like osteoporosis and osteoarthritis.
• Fat mass and obesity-associated protein (FTO), an m6A demethylase, is increasingly recognized as a critical regulator in skeletal biology.
• FTO's role is context-dependent, exhibiting diverse effects based on cell type, disease stage, and molecular interactions.

Purpose of the Study:

• To review current evidence on the multifaceted roles of FTO in skeletal biology.
• To summarize FTO's involvement in osteoblast differentiation, osteoclast activity, and bone marrow mesenchymal stem cell (BMSC) lineage commitment.
• To discuss FTO's impact on cartilage homeostasis, bone malignancies, and metastasis.

Main Methods:

• This study is a narrative review of existing scientific literature.
• It synthesizes findings from preclinical studies investigating FTO's function in various skeletal contexts.
• The review analyzes evidence regarding FTO's therapeutic potential and translational challenges.

Main Results:

• FTO exhibits context-specific effects, acting as neither uniformly pro-osteogenic nor disease-promoting.
• Evidence highlights FTO's influence on osteoblasts, osteoclasts, BMSCs, cartilage, and bone cancers.
• The current evidence base for FTO's role in skeletal diseases is largely preclinical.

Conclusions:

• FTO is a promising therapeutic target for skeletal diseases due to its regulatory roles.
• Further clinical validation is required to confirm FTO's efficacy and safety in therapeutic applications.
• Interpreting current preclinical findings requires caution due to the need for clinical translation.