Functional diversity of fibroblast growth factors in bone formation

Area of Science:

• Endocrinology
• Cell Biology
• Orthopedics

Background:

• Fibroblast growth factors (FGFs) are critical regulators of bone formation, with 22 members classified into canonical, hormone-like, and intracellular subfamilies.
• Canonical FGFs (e.g., FGF2) and hormone-like FGFs signal via FGF receptors (FGFRs), influencing bone development through precise spatiotemporal control.
• Intracellular FGFs are mainly associated with the nervous system, while canonical and hormone-like FGFs have distinct roles in skeletal biology.

Purpose of the Study:

• To review the multifaceted roles of FGF signaling in bone formation.
• To elucidate the reciprocal functions of FGFs, distinguishing between local and systemic effects on bone metabolism.
• To highlight the importance of FGF23 in phosphate homeostasis and its impact on bone mineralization.

Main Methods:

• Literature review of genetic loss-of-function and gain-of-function studies on FGF signaling in bone.
• Analysis of research on the classification and signaling mechanisms of FGF subfamilies.
• Synthesis of findings on FGF23 expression and its systemic effects on phosphate and vitamin D metabolism.

Main Results:

• Canonical FGFs, like FGF2, are essential for positive bone formation through localized signaling.
• Hormone-like FGF23, produced by osteocytes/osteoblasts, exerts systemic effects, lowering serum phosphate and inhibiting vitamin D activation, which can impair bone mineralization.
• FGF signaling exhibits both anabolic and catabolic influences on bone, depending on the specific FGF member and its mode of action.

Conclusions:

• FGFs are key regulators of bone formation, acting through both local and systemic mechanisms.
• FGF23 plays a critical role in systemic mineral ion homeostasis, with significant implications for bone health and disease.
• Precise regulation of FGF/FGFR signaling is vital for maintaining skeletal integrity and function.