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

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.

Gold Nanoparticles Combined Human β-Defensin 3 Gene-Modified Human Periodontal Ligament Cells Alleviate Periodontal Destruction via the p38 MAPK Pathway

“…The three cell growth phases, lag, log (exponential), and plateau, were observed from the cell growth curve measured by CCK8. Our team has already proved that rPDLCs transfected with Ad-hBD3 could successfully express hBD3 ( Li et al, 2020 ). Fluorescence images showed rPDLCs transfected with Ad-hBD3 after cultured for 3 days ( Figure 4B ).…”

“…In our former study, hPDLCs transfected by adenovirus containing the hBD3 gene were observed to express the hBD3 protein for at least 7 days. After transfection, Ad-hBD3-hPDLCs showed higher expression of osteogenic-related genes and proteins than normal hPDLCs in inflammatory microenvironments ( Li et al, 2020 ).…”

“…The recombinant adenovirus carried the human beta defensin-3 gene (Ad-hBD3) was purchased from the GenePharma company (GenePharma, Shanghai, China). The hPDLCs were transfected with Ad-hBD3 according to our former study ( Li et al, 2020 ).…”

“…Therefore, our team previously synthesized adenovirus vectors containing the hBD3 gene and successfully transfected them into hPDLCs. The enhancement effects of osteogenic differentiation and bone regeneration have also been observed after hBD3 gene transfection ( Li et al, 2020 ).…”

“…The process of osteogenic differentiation involves the activation of multiple signaling pathways ( Long et al, 2019 ; Ohashi et al, 2019 ). Among these, the p38 MAPK pathway is one of the critical pathways; it has been reported to regulate the osteogenesis process in various cells, including hPDLCs ( Yi et al, 2010 ; Ren et al, 2013 ; Li et al, 2020 ). There are few reports about hBD3 and osteogenesis, yet other cationic antimicrobial peptides like LL37 were demonstrated to affect the proliferation and differentiation of MC3T3-E1 cells ( Shen et al, 2019 ) and could enhance bone regeneration in a rat calvarial bone defect through p38 MAPK pathways ( Kittaka et al, 2013 ).…”