Fibroblast growth factor 23: Regulation, signalling and systemic links between bone, metabolism and inflammation

Area of Science:

• Endocrinology and Metabolism
• Bone Biology
• Molecular Signaling

Background:

• Fibroblast growth factor 23 (FGF23) is a critical bone-derived hormone.
• It regulates phosphate and mineral homeostasis.
• Emerging evidence highlights FGF23's broader roles in metabolism, inflammation, and disease.

Purpose of the Study:

• To provide a comprehensive overview of FGF23 biology.
• To integrate knowledge of FGF23's regulation, processing, signaling, and actions.
• To examine FGF23's adaptive and maladaptive roles in various physiological and pathological contexts.

Main Methods:

• Literature review and synthesis of experimental and clinical evidence.
• Focus on FGF23's transcriptional and post-translational regulation.
• Analysis of canonical (α-Klotho dependent) and non-canonical signaling pathways.

Main Results:

• FGF23 is produced by osteocytes/osteoblasts, released as intact or cleaved forms.
• Canonical signaling involves FGF receptors and α-Klotho.
• FGF23 impacts bone mineralization, phosphocalcium metabolism, energy homeostasis, inflammation, cardiovascular health, CKD, cancer, and nervous system function.

Conclusions:

• FGF23 is a multifunctional hormone linking bone to systemic networks.
• Its actions are context-dependent, with both beneficial and detrimental roles.
• Understanding FGF23 biology offers therapeutic intervention opportunities.