Pigment epithelium-derived factor modulates periodontal homeostasis in mice and induces osteogenic differentiation of human periodontal ligament fibroblasts. (3rd September 2022)

• Record Type: Journal Article
• Authors: Xu, Cheng; Du, Yu; Tian, Jun; Liu, Chang; Huang, Yihua; Zhou, Ti; Ning, Yang
• Is Part Of: Connective tissue research. Volume 63:Number 5(2022)
• Page Start: 485
• Page End: 497
• Publication Date: 2022-09-03
• Subjects: Pigment epithelium-derived factor -- periodontal homeostasis -- periodontal ligament fibroblasts -- osteogenesis -- osteogenic differentiation; Connective tissues -- Periodicals; 616.770072
• DOI: 10.1080/03008207.2021.2025224
• Languages: English
• ISSNs: 0300-8207

Abstract

ABSTRACT: Aim: The aim of this study was to investigate the influence of pigment epithelium-derived factor (PEDF) on periodontal homeostasis in mice and the osteogenic differentiation of human periodontal ligament fibroblasts (PDLFs). Materials and Methods: Micro-computed tomography and histology were performed to compare the alveolar bone volume, density, and bone-related markers between PEDF-deficient (PEDF −/− ) and wild-type (WT) mice. Furthermore, after recombinant human PEDF treatment, the PDLF viability and osteogenic differentiation were examined using the 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide (MTT) assay, alkaline phosphatase (ALP) activity assay, Von Kossa staining, Alizarin red staining, real-time quantitative polymerase chain reaction (qRT-PCR), and immunoblotting. Results: The alveolar bone volume and density of PEDF −/− mice were significantly lower than those of the WT mice. Higher receptor activator for nuclear factor-κB ligand (RANKL) expression and lower osteoprotegerin (OPG) expression levels were observed in the PEDF −/− group. Moreover, PEDF treatment did not affect the PDLF proliferation. PEDF dose-dependently improved mineral deposition. Compared with the control group, 250 ng/mL PEDF promoted OPG mRNA expression in PDLFs on Day 3 but inhibited RANKL, Wnt5a, GSK3b mRNA, and non-phosphorylated β-catenin protein expression. However, 250 ng/mL PEDF had no significant effect on the expression of Wnt3a. On Day 7, after culture with 250 ng/mL PEDF in osteogenic medium, the ALP and RUNX2 protein levels were upregulated. VEGF protein expression was reduced in a dose-dependent manner after PEDF stimulation. The PEDF protein expression increased as the osteogenic induction time increased. Conclusion: PEDF gene knockout suppresses periodontal homeostasis in mice, and PEDF treatment induces PDLF osteogenic differentiation in vitro .