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

BACKGROUND & OBJECTIVE: Notch 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-alpha, IL-17, IL-1beta, and IL-6) in patients with peri-implant diseases. The aforementioned markers' expression was evaluated in patients with different RANKL/OPG ratios. METHODS: Fifty 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). RESULTS: RANKL-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-1beta (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). CONCLUSIONS: Notch2 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-1beta and IL-6 might provide an osteoclastogenic environment in PI RANKL-predominant lesions.