The role of fibroblast growth factor-2 in modulating the differentiation of periodontal ligament and alveolar bone-derived stem cells.

Arch Oral Biol

Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, United States; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI, United States. Electronic address:

Published: September 2024

AI Article Synopsis

  • The study explored how different concentrations of Fibroblast Growth Factor-2 (FGF-2) affect the differentiation of human periodontal ligament stem cells (hPDLSCs) and alveolar bone-derived stem cells (haBMSCs).
  • At low FGF-2 levels, hPDLSCs showed signs of osteogenic differentiation, but higher concentrations shifted their development towards a fibroblastic phenotype.
  • All concentrations of FGF-2 enhanced alkaline phosphatase (ALP) activity in haBMSCs, with optimal mineralization observed at moderate concentrations (5-20 ng/mL), highlighting the importance of precise growth factor dosing for effective stem cell differentiation in dental applications.

Article Abstract

Objective: This study examined how range concentrations of Fibroblast Growth Factor-2 (FGF-2) influence the differentiation and activity of human-derived periodontal ligament (hPDLSCs) and alveolar bone-derived stem cells (haBMSCs).

Design: hPDLSCs and haBMSCs were cultured with varying concentrations of FGF-2 (0, 1, 2.5, 5, 10, 20 ng/mL) and monitored for osteogenic differentiation through alkaline phosphatase (ALP) activity and quantification of gene expression (qRT-PCR) for osteogenesis markers. Additionally, alizarin red staining and a hydroxyproline colorimetric assay evaluated and quantified osteogenic matrix mineralization and collagen deposition. Statistical analyses were performed using one-way ANOVA or two-way ANOVA for multiple comparisons between groups.

Results: At low FGF-2 concentrations, hPDLSCs differentiated toward an osteogenic lineage, whereas higher concentrations of FGF-2 inhibited osteogenesis and promoted fibroblastic differentiation. The effect of FGF-2 at the lowest concentration tested (1 ng/mL) led to significantly higher ALP activity than osteogenically induced positive controls at early time points and equivalent RUNX2 expression at early and later time points. FGF-2 supplementation of haBMSC cultures was sufficient, at all concentrations, to increase ALP activity at an earlier time point. Mineralization of haBMSC cultures increased significantly within 5-20 ng/mL FGF-2 concentrations under basal growth media conditions (α-minimal essential medium supplemented with 15 % fetal bovine serum and 1 % penicillin/streptomycin).

Conclusions: FGF-2 has a dual capacity in promoting osteogenic and fibroblastic differentiation within hPDLSCs contingent upon the dosage and timing of administration, alongside supporting osteogenic differentiation in haBMSCs. These findings underscore the need for precision growth factors dosing when considering the design of biomaterials for periodontal regeneration.

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Source
http://dx.doi.org/10.1016/j.archoralbio.2024.106027DOI Listing

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