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• Local growth factor delivery is a viable option to change the microenvironment of the periodontium to facilitate repair. • FGF family members increased migration, while TGF-β isoforms increased α-SMA expression and matrix production. • Based on Effects, we investigated the combined effect of TGF-β3 and FGF-2 on gingival and periodontal ligament fibroblasts. • Combinatory treatment with TGF-β3+FGF-2 enhanced migration and fibronectin levels in both gingival and periodontal ligament fibroblasts. • TGF-β3+FGF-2 regulate cell phenotype simultaneously through distinct p-SMAD2/3 and p-ERK pathways. • Soft tissue healing could be enhanced with local delivery of TGF-β3+FGF-2 Release of growth factors in the tissue microenvironment is a critical process in the repair and regeneration of periodontal tissues, regulating fibroblast behavior and phenotype. As a result of the complex architecture of the periodontium, distinct fibroblast populations in the periodontal ligament and gingival connective tissue exist in close proximity. Growth factor therapies for periodontal regeneration have gained traction, but quantification of their effects on multiple different fibroblast populations that are required for repair has been poorly investigated. In this study, we examined the effects of TGF-β1, TGF-β3, FGF-2, and FGF-9 on human gingival fibroblasts (hGF) and human periodontal ligament cells (hPDL), as well as the combined effects of TGF-β3 and FGF-2. We show that FGF-2 enhances cell migration while TGF-β1 and TGF-β3 promotes matrix production, and TGF-β1 promotes fibroblast to myofibroblast transition. Interestingly, the combination of TGF-β3 and FGF-2, acting through both p-SMAD3 and p-ERK pathways, mitigates the inhibitory effects of TGF-β3 on migration in hPDL cells, suggesting synegystic and complimentary effects of FGF-2 and TGF-β3. Additionally, fibronectin production in hGF increased when treated with the combined TGF-β3+FGF-2 compared to FGF-2 alone, indicating that the effects of TGF-β3 in promoting extracellular matrix production are still active in the combined treatment condition. Finally, our study highlights that FGF-9 did not influence migration, α-SMA expression, or extracellular matrix production in either cell type, emphasizing the unique roles of specific growth factors in cellular responses. The synergistic effects observed with combined TGF-β3 and FGF-2 treatments present promising avenues for further research and clinical advancements in regenerative medicine.
Guo et al. (Sat,) studied this question.