Notch signalling cascade and proinflammatory mediators in peri‐implant lesions with different RANKL/OPG ratios—An observational study

Abstract

AbstractBackground & ObjectiveNotch signaling pathway has been linked to bone loss in periodontitis and peri‐implantitis. This research aimed to determine the Notch signaling molecules expression levels (Notch1, Notch2, Jagged1, Hes1, and Hey1), along with bone remodeling mediators (RANKL and OPG) and proinflammatory cytokines (TNF‐α, IL‐17, IL‐1β, and IL‐6) in patients with peri‐implant diseases. The aforementioned markers' expression was evaluated in patients with different RANKL/OPG ratios.MethodsFifty patients with peri‐implantitis (PI group) and 45 patients with peri‐implant mucositis (PM group) were enrolled. Relative gene expression levels of investigated molecules were determined by reverse transcriptase‐real‐time polymerase chain reaction. On the basis of RANKL/OPG ratio, all peri‐implant lesions were divided into subgroups: RANKL‐predominant (RANKL > OPG) and OPG‐predominant (RANKL < OPG). Clinical periodontal parameters (probing depth‐PD, bleeding on probing‐BOP, clinical attachment level‐CAL and plaque index‐PLI), were recorded for each patient around every tooth, and around placed implants (PDi, BOPi, CALi, PLIi).ResultsRANKL‐predominant PM patients exhibited higher expression levels of Notch2 (p = .044) and Hey1 (p = .005) compared to OPG‐predominant lesions. In all RANKL‐predominant cases, Hey1 (p = .001), IL‐1β (p = .005), IL‐6 (p = .002) were overexpressed in PI comparing to PM, accompanied with significantly higher PDi, CALi and PLIi in PI than PM (p = .001, p = .001 and p = .009).ConclusionsNotch2 upregulation in RANKL‐predominant PM lesions could be an important contributor to alveolar bone resorption and represent a predictor of PM to PI transition. Similarly, the overexpression of IL‐1β and IL‐6 might provide an osteoclastogenic environment in PI RANKL‐predominant lesions.