Fibroblast Growth Factor Signaling in Skeletal Development and Repair

Fibroblast growth factors (FGFs) constitute a family of 22 ligands that engage tyrosine kinase FGF receptors (FGFR1–4) to regulate skeletal patterning, cartilage formation and bone homeostasis. During embryonic development, FGF signalling guides limb bud outgrowth, condensation of mesenchymal progenitors and differentiation of chondrocytes and osteoblasts. In the mature skeleton, FGFs modulate the balance between bone formation and resorption, influence fracture-healing cascades and contribute to the maintenance of articular cartilage. Canonical FGFs often act locally through paracrine loops, whereas endocrine FGFs (for example FGF19, FGF21, FGF23) regulate mineral metabolism and systemic phosphate homeostasis. Downstream effectors such as MAPKs, PI3K–AKT and STATs intersect with Wnt and Indian hedgehog pathways to fine-tune cell proliferation, matrix production and maturation. Dysregulated FGF–FGFR signalling underpins skeletal dysplasias, osteoarthritis and delayed repair, yet controlled activation of specific ligands offers routes to targeted therapies, biomaterial integration and stem-cell-based regeneration.

Research from Nature Portfolio

Recent studies have shown that selective loss of FGFR3 in adult chondrocytes disrupts cartilage homeostasis in the temporomandibular joint, producing osteoarthritis-like pathology. Deletion of Fgfr3 in mature chondrocytes led to elevated expression of hypertrophic markers (COL10, MMP13, ADAMTS5) and enhanced apoptosis, accompanied by upregulation of Runx2 and Indian hedgehog signalling. Pharmacological inhibition of the hedgehog pathway partially restored lubricin levels and improved surface integrity, revealing a critical FGFR3–IHH signalling axis that preserves articular cartilage architecture and suggesting a potential therapeutic avenue for degenerative joint disease.

Fibroblast Growth Factor Signaling in Skeletal Development and Repair publication trend

The graph below shows the total number of articles in fibroblast growth factor signaling in skeletal development and repair across all publications each year (not limited to Nature Index journals).

Technical terms

Fibroblast growth factor (FGF): A family of signalling proteins that bind FGFRs to regulate cell proliferation, differentiation and tissue patterning.

FGF receptor (FGFR): A tyrosine kinase receptor with four main isoforms (FGFR1–4) that mediates FGF ligand signalling.

Osteoblast: A bone-forming cell responsible for synthesising and mineralising extracellular matrix.

Chondrocyte: A cartilage-producing cell that secretes collagen and proteoglycans within cartilage tissue.

Mesenchymal stem cell (MSC): A multipotent progenitor capable of differentiating into osteoblasts, chondrocytes and other mesodermal lineages.

References

1. Role of signaling pathways in age-related orthopedic diseases: focus on the fibroblast growth factor family. Military Medical Research (2024).
2. miR-181a/MSC-Loaded Nano-Hydroxyapatite/Collagen Accelerated Bone Defect Repair in Rats by Targeting Ferroptosis Pathway. Journal of Functional Biomaterials (2024).
3. Overexpression of Fgf18 in cranial neural crest cells recapitulates Pierre Robin sequence in mice. Frontiers in Cell and Developmental Biology (2024).
4. Conditional Deletion of Fgfr3 in Chondrocytes leads to Osteoarthritis-like Defects in Temporomandibular Joint of Adult Mice. Scientific Reports (2016).