Osteopontin is essential for IL-1β production and apoptosis in peri-implantitis

Abstract

Background and purpose: Peri-implantitis is caused by a cascade of host and microbial factors leading to an oral inflammatory disease. The inflammation proliferates into supporting tissues surrounding implants and may finally lead to a complete loss of osseointegration. Being a phosphorylated glycoprotein secreted by immunocompetent cells, osteopontin (OPN) is involved in the differentiation of odontoblast-like cells during pulpal healing following tooth transplantation and the secretion of type I collagen in reparative dentin. But the production and function of OPN in peri-implantitis has not been thoroughly evaluated.

Materials and methods: Peri-implant crevicular fluid (PICF) was collected from 28 healthy implants patients and 28 peri-implantitis patients to determine the expression of OPN in response to the inflammation of peri-implantitis by Western-blot, Enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. THP-1 macrophages infected by Porphyromonas gingivalis were chosen to reveal the production and function of OPN in peri-implantitis by immunofluorescence staining, quantitative polymerase chain reaction (RT-PCR), and Western-blot.

Results: Results showed that OPN increased in most PICF of peri-implantitis patients and in THP-1 macrophages stimulated with P. gingivalis. The expression of OPN in response to P. gingivalis decreased at mRNA and protein levels when exposed to either the lectin-type oxidized LDL receptor 1 (LOX-1) neutralizing antibody or inhibitor pretreatment in THP-1 macrophages. P. gingivalis induces OPN through the Erk1/2 MAPK dependent pathway. OPN neutralization decreased interleukin 1 beta (IL-1β) expression on P. gingivalis infection, and the lower IL-1β mRNA and protein levels were rescued by human osteopontin recombinant protein (rhOPN) in THP-1 macrophages. RhOPN suppressed P. gingivalis induced apoptosis of the mitochondrial pathway in THP-1 macrophage.

Conclusions: Overall, the results of this study provide insight into the essential roles of OPN for IL-1β production and apoptosis in peri-implantitis, as supported by the evidence from the study of patient's PICF and cell culture experiments.

Keywords: IL-1β; LOX-1; apoptosis; osteopontin; peri-implantitis.