Fibroblast growth factors (FGFs) are a family of growth factors involved in various biological processes including development, tissue repair, and metabolism. They are crucial in embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. FGFs are characterized by their ability to bind to heparin and heparan sulfate, which stabilizes them and enhances their interactions with fibroblast growth factor receptors (FGFRs). The biochemical composition of FGFs can be summarized as follows:

  1. Amino Acid Sequence: FGFs are composed of a single polypeptide chain ranging from approximately 150 to 300 amino acids. The amino acid sequence varies among different FGFs, but they share a conserved core region that is crucial for their biological activity.
  2. Core Structure: The conserved core region, also known as the “FGF core domain,” consists of about 120 amino acids forming a β-trefoil structure. This structure is composed of 12 β-strands arranged in three sets of four β-strands, forming a stable and compact domain essential for receptor binding and biological function.
  3. Heparin-binding Domain: FGFs possess specific domains that enable them to bind to heparin and heparan sulfate proteoglycans. This binding is important for their stability, distribution, and interaction with FGFRs.
  4. Isoelectric Point (pI): FGFs generally have a basic isoelectric point due to the presence of positively charged amino acids (lysine and arginine) in the heparin-binding domain, which facilitates their interaction with the negatively charged heparin sulfate.
  5. Post-translational Modifications: FGFs may undergo various post-translational modifications, including glycosylation, phosphorylation, and proteolytic cleavage, which can affect their stability, activity, and interactions with receptors.
  6. Receptor Binding: FGFs exert their biological effects by binding to and activating specific FGFRs, which are tyrosine kinase receptors. The binding induces receptor dimerization and autophosphorylation, leading to the activation of downstream signaling pathways that regulate cell proliferation, differentiation, and survival.

Types and Receptors

FGF Family: There are 22 known FGFs in humans, labeled FGF1 through FGF23 (FGF15 in humans is analogous to FGF19 in mice). They are divided into subfamilies based on their sequence similarity and functions.
FGF Receptors (FGFRs): FGFs exert their effects by binding to specific FGF receptors, which are a family of receptor tyrosine kinases (FGFR1 through FGFR4). Upon binding, these receptors dimerize and autophosphorylate, triggering downstream signaling pathways.


Embryonic Development: FGFs play critical roles in the formation of limbs, brain development, and organogenesis. They are involved in patterning, cell differentiation, and proliferation.
Tissue Repair and Regeneration: FGFs are important for wound healing and tissue regeneration. For instance, FGF2 (basic FGF) is known for its role in angiogenesis, the growth of new blood vessels from pre-existing ones.
Metabolism: Certain FGFs, like FGF19 and FGF21, act as hormones regulating metabolism. They influence bile acid synthesis, lipid metabolism, and glucose homeostasis.

Mechanisms of Action

FGFs signal through FGFRs by:

Autocrine and Paracrine Signaling: Acting on the same cell that produces them or on neighboring cells.
Endocrine Signaling: Some FGFs, like FGF19, FGF21, and FGF23, can function in an endocrine manner, traveling through the bloodstream to distant target organs.

Clinical Relevance

Cancer: Aberrant FGF signaling is implicated in various cancers, promoting tumor growth and metastasis. FGFR inhibitors are being explored as cancer therapies.
Bone Disorders: Mutations in FGFRs can lead to skeletal disorders like achondroplasia and craniosynostosis syndromes.
Metabolic Diseases: FGF21 analogs are being investigated for treating metabolic diseases like obesity and type 2 diabetes.

Research and Therapeutic Potential

Regenerative Medicine: FGFs are used in regenerative therapies to promote tissue repair and healing.
Drug Development: FGFR inhibitors and FGF analogs are under development for treating various conditions ranging from cancer to metabolic disorders.

Role of fibroblast growth factors in periodontal regeneration

Fibroblast growth factors (FGFs) play a significant role in periodontal regeneration, which involves the restoration of the tooth-supporting structures that are damaged due to periodontal diseases. 

Stimulation of Cell Growth: FGFs, particularly FGF2 (basic FGF), promote the proliferation of various cell types involved in periodontal regeneration, including fibroblasts, osteoblasts, and cementoblasts.
Enhancing Differentiation: FGFs aid in the differentiation of progenitor cells into specific cell types needed for regenerating periodontal tissues.

New Blood Vessel Formation: FGFs are potent angiogenic factors. They stimulate the formation of new blood vessels, which is crucial for providing nutrients and oxygen to the regenerating tissues, facilitating the healing process.

Extracellular Matrix Formation:
Matrix Production: FGFs promote the production of extracellular matrix components like collagen and glycosaminoglycans. This is essential for the structural integrity and function of the regenerated periodontal tissues.

Bone Regeneration:
Osteogenesis: FGFs stimulate osteoblast activity and bone formation, which is vital for regenerating alveolar bone lost due to periodontal disease.

Wound Healing:
Accelerating Healing: By promoting cell migration and proliferation, FGFs accelerate the wound healing process in periodontal tissues.

Mechanisms of Action

Receptor Binding: FGFs exert their effects by binding to specific FGF receptors (FGFRs) on the surface of target cells, triggering intracellular signaling pathways such as the MAPK, PI3K/Akt, and PLCγ pathways.
Paracrine and Autocrine Signaling: FGFs can act in a paracrine manner, affecting nearby cells, or in an autocrine manner, affecting the cells that produce them.

Clinical Applications

Topical Application: FGF2 is often used in topical formulations to enhance periodontal regeneration. Studies have shown that topical application of FGF2 can significantly improve the regeneration of periodontal tissues.
Biomaterials and Scaffolds: FGFs are incorporated into biomaterials and scaffolds used in periodontal surgeries. These scaffolds provide a framework for cell attachment and growth, while FGFs promote tissue regeneration.
Gene Therapy: Gene therapy approaches are being explored to deliver FGF genes directly to periodontal sites, aiming for sustained and localized production of FGFs to enhance regeneration.

Research and Evidence

Preclinical Studies: Animal studies have demonstrated the effectiveness of FGFs in promoting periodontal regeneration. For example, FGF2 has been shown to enhance the regeneration of periodontal ligament, alveolar bone, and cementum in animal models.
Clinical Trials: Clinical trials have indicated that FGF2 can improve clinical outcomes in patients with periodontal disease, leading to better attachment levels and bone regeneration compared to conventional treatments.

Challenges and Considerations

Delivery Methods: Effective and controlled delivery of FGFs to the periodontal site remains a challenge. Innovations in drug delivery systems, such as sustained-release formulations and targeted delivery mechanisms, are being investigated.
Dosage and Safety: Determining the optimal dosage and ensuring the safety of FGF treatments are crucial for their successful application in periodontal therapy.


Fibroblast growth factors, particularly FGF2, play a pivotal role in periodontal regeneration by promoting cell proliferation, differentiation, angiogenesis, extracellular matrix formation, and bone regeneration. Their application in periodontal therapy holds promise for improving the outcomes of treatments for periodontal disease, with ongoing research focused on optimizing delivery methods and ensuring safety and efficacy.


Periobasics: A Textbook of Periodontics and Implantology

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