The Regenerative Potential of bFGF in Dental Pulp Repair and Regeneration

Abstract

Regenerative endodontic therapy intends to induce the host’s natural wound-healing process, which can restore the vitality, immunity, and sensitivity of the inflammatory or necrotic pulp tissue destroyed by infection or trauma. Myriads of growth factors are critical in the processes of pulp repair and regeneration. Among the key regulatory factors are the fibroblast growth factors, which have turned out to be the master regulators of both organogenesis and tissue homeostasis. Fibroblast growth factors, a family composed of 22 polypeptides, have been used in tissue repair and regeneration settings, in conditions as diverse as burns, ulcers, bone-related diseases, and spinal cord injuries. Meanwhile, in dentistry, the basic fibroblast growth factor is the most frequently investigated. Thereby, the aim of this review is 2-fold: 1) foremost, to explore the underlying mechanisms of the bFGF in dental pulp repair and regeneration and 2) in addition, to shed light on the potential therapeutic strategies of the bFGF in dental pulp–related clinical applications.

bFGF stimulated plasminogen activation factors, but inhibited alkaline phosphatase and SPARC in stem cells from apical Papilla: Involvement of MEK/ERK, TAK1 and p38 signaling

“…bFGF stimulated the proliferation of SCAP under serum-free conditions [18] . bFGF also stimulates cell stemness, DNA synthesis, and the proliferation of dental pulp cells, but inhibits apoptosis [10] , [31] , [34] , [35] , indicating the general growth-stimulating effect of bFGF.…”

“…These events are differentially regulated through receptor activation and signaling [32] . Four FGF receptors (FGFR1, 2, 3, and 4), are differentially expressed in different kinds of tissues and organs [10] , but upstream stimulators and downstream signaling molecules (e.g., phospholipase C gamma, leukemia inhibitory factor-signal transducers, activators of transcription [STAT], mitogen-activated protein kinase [MAPK], and phosphatidylinositol-4,5-bisphosphate 3-kinase [PI3K]-AKT) mediating different FGFR activation show some differences and remain to be clarified [10] , [32] , particularly in SCAP. We recently demonstrated FGFR1 and FGFR2 mRNA expression in SCAP and human dental pulp cells [18] , [31] .…”

“…These growth factors and many other pro-inflammatory cytokines may promote wound healing and angiogenic and neurogenic responses by provoking and controlling various cell activities such as metabolism, mitogenesis, chemotaxis, and differentiation of SCAP [8] . The family members of FGFs play pivotal roles in the regulation of cell proliferation, migration,t and differentiation during organ development via the activation of various fibroblast growth factor receptors (FGFRs) [10] . bFGF may be involved in bone remodeling, osteogenesis, and cementogenesis, which are crucial for the regeneration of periodontal and periapical tissues [11] , [12] .…”

Biomolecule-Mediated Therapeutics of the Dentin–Pulp Complex: A Systematic Review

“…BFGF binds to tyrosine kinase FGF receptors 1–4 on the cell membrane, and phosphorylation occurs. Then, a cascade of intracellular signaling pathways, such as the RAS-MAPK, PI3K-AKT, PLCγ, and JAK/STAT, initiate cell migration, proliferation, and differentiation [ 49 ]. Five included studies used bFGF alone or in combination with other signaling molecules for pulp regeneration [ 22 , 31 , 32 , 34 , 35 ].…”

Genome wide analysis of dexamethasone stimulated mineralization in human dental pulp cells by RNA sequencing

“…Notably, FGF‐2 was found to be enhanced by dexamethasone by over 16‐fold compared to the control. Indeed, FGF‐2, a growth factor governing organogenesis and tissue homeostasis, plays an essential role in stemness maintenance and regulates dental pulp cells in a stage‐specific manner 64,65 . Another study further explored its role in odontoblast differentiation in αSMACre‐tdTomato mice model and concluded that early and pulsed exposure to FGF‐2 facilitated the differentiation of odontoblasts and promoted the formation of reparative dentin devoid of osteoblasts 66 .…”