Human \u03b2-defensin 3 gene modification promotes the osteogenic differentiation of human periodontal ligament cells and bone repair in periodontitis

Lingjun Li,Yin Xiao,Rixin Chen,Yangheng Zhang,Fuhua Yan,Jing Zhou,Han Jiang

doi:10.1038/s41368-020-0078-6

Abstract

Efforts to control inflammation and achieve better tissue repair in the treatment of periodontitis have been ongoing for years. Human β-defensin 3, a broad-spectrum antimicrobial peptide has been proven to have a variety of biological functions in periodontitis; however, relatively few reports have addressed the effects of human periodontal ligament cells (hPDLCs) on osteogenic differentiation. In this study, we evaluated the osteogenic effects of hPDLCs with an adenoviral vector encoding human β-defensin 3 in an inflammatory microenvironment. Then human β-defensin 3 gene-modified rat periodontal ligament cells were transplanted into rats with experimental periodontitis to observe their effects on periodontal bone repair. We found that the human β-defensin 3 gene-modified hPDLCs presented with high levels of osteogenesis-related gene expression and calcium deposition. Furthermore, the p38 MAPK pathway was activated in this process. In vivo, human β-defensin 3 gene-transfected rat PDLCs promoted bone repair in SD rats with periodontitis, and the p38 mitogen-activated protein kinase (MAPK) pathway might also have been involved. These findings demonstrate that human β-defensin 3 accelerates osteogenesis and that human β-defensin 3 gene modification may offer a potential approach to promote bone repair in patients with periodontitis.

Highlights

Periodontitis, a chronic inflammatory disease induced by dental plaque, damages the integrity of tooth-supporting tissues.[1]
multiplicity of infection (MOI) 150 was chosen for the following experiments. human periodontal ligament cells (hPDLCs) transfected with Ad-hBD3 showed high hBD3 gene and protein expression levels (Fig. 1c) from day 3 to day 7
1 μg·mL−1 E. coli LPS was chosen to create the inflammatory microenvironment, because LPS was proven in previous studies to induce an hPDLC inflammatory response.[34,35]

Summary

Introduction

Periodontitis, a chronic inflammatory disease induced by dental plaque, damages the integrity of tooth-supporting tissues.[1] It can disturb normal bone metabolism and eventually result in alveolar bone loss.[2] According to epidemiological investigations, at least one-half of the world’s population suffers from periodontitis, and it has become the eleventh disease among global diseases that cause short- or long-term loss of health.[3] Poor periodontal condition is a major problem that affects the oral health of people in China.[4] Inflammatory responses and bone loss due to periodontitis have become the most critical and challenging problems to be solved for individuals to achieve healthy periodontium.[5,6]. HBD3 plays a pivotal role in cell proliferation and differentiation. hBD3 potentially promotes the proliferation of periodontal ligament (PDL) fibroblasts[13] and the osteogenic differentiation of osteoblast-like human osteosarcoma cells (MG63 cells).[14]

Methods

Results

Conclusion