WNT-5a and SOST Levels in Gingival Crevicular Fluid Depend on the Inflammatory and Osteoclastogenic Activities of Periodontal Tissues

Abstract

Background and Objectives: Wnt signaling leads to stimulation of osteoblasts and it reduces osteoclastogenesis and bone resorption via the regulation of the osteprotegrin and receptor activator of nuclear factor kappa-Β ligan (RANKL). Wnt signaling pathways are regulated by their physiological antagonists such as sclerostin (SOST) as well as WNT-5a. The aim of this study was to determine the total amount of Sclerostin and WNT-5a in the gingival crevicular fluid (GCF) in sites with a continuum from a healthy to diseased periodontium. Materials and Methods: In this cross-sectional study, a total of 20 patients with generalized periodontitis, 10 subjects with gingivitis as well as 14 individuals with a healthy periodontium were recruited upon clinical and radiographic periodontal examination. In patients diagnosed with periodontitis, GCF samples were collected from periodontitis, gingivitis and healthy sites, while gingivitis patients provided samples from gingivitis and healthy sites. In healthy patients, only healthy sites were sampled. Protein total amount of SOST and WNT-5a were quantified by sandwich enzyme-linked immunosorbent assay (ELISA). Results: A total of 108 GCF samples were collected from a total of 44 individuals. When all periodontitis (n = 51), gingivitis (n = 12) and healthy (n = 45) sites were analyzed regardless of the patient diagnosis, periodontitis sites demonstrated significantly elevated WNT-5a total amounts (p = 0.03) when compared to gingivitis sites. Gingivitis sites demonstrated a trend of more total SOST (p = 0.09) when compared to periodontitis and healthy sites. Within each patient diagnostic category, sites showed similar SOST and WNT-5a total amounts (p > 0.05). Conclusions: WNT-5a levels in GCF depend on the stage of periodontitis sites. SOST trended higher in the GCF of gingivitis sites but similar in chronic periodontitis and healthy sites. WNT-5a and SOST play a crucial role in periodontal tissue remodeling and depend on the inflammatory and osteoclastogenic activities.

Exosomes Derived From Human Gingival Mesenchymal Stem Cells Attenuate the Inflammatory Response in Periodontal Ligament Stem Cells

“…Wnt5a is usually at a low expression level in healthy adult tissues compared to those of the embryo ( Yap et al, 2014 ), but the dysregulation of Wnt5a usually results in it being overexpressed, resulting in a number of diseases. It was significantly elevated in gingival crevicular fluid at periodontitis sites when compared to healthy gums ( Chatzopoulos et al, 2021 ). The expression of Wnt5a was upregulated in the inflammatory microenvironment simulated by LPS in vitro ( He et al, 2014 ), which was in agreement with our results.…”

Expression of Wnt signaling agonists and antagonists in periodontitis and healthy subjects, before and after non‐surgical periodontal treatment: A systematic review

“…and the Wnt‐5a GCF levels were significantly lower in gingivitis than in periodontitis and healthy sites 50 . No differences were observed in another study 51 . Based on the available data from two studies, no significant correlation between Wnt5a levels and clinical parameters was detected 50,51 …”

“…In addition, a fifth study demonstrated that when generalized moderate and severe periodontitis was considered, SOST exhibited significantly higher amounts in the GCF of periodontitis sites 50 . No significant differences between healthy and periodontitis sites were found in only one study 51 . When the correlation between SOST and clinical parameters was evaluated, significant positive findings were identified in five investigations 45,47,48,50,57 .…”

“…Five studies were conducted in China, 46,52,54,59,60 3 in the USA, 50,51,55 2 in India, 48,58 2 in Turkey, 45,47 and the others were from Brazil, 57 Chile, 49 Thailand, 56 and Iran 53 . The majority of the studies were case–control studies ( n = 12), 45,50–60 while randomized clinical trials and non‐randomized clinical interventional studies were also included. The total number of periodontitis patients in the test groups ranged from 11 to 44 (periodontitis group), whereas the control group included 5 to 29 periodontally healthy individuals (healthy group).…”

“…Eight studies examined GCF samples only, 45–51,53 two studies included both GCF and gingival tissue samples, 59,60 and one study sampled gingival tissue and serum, 57 whereas the remaining five studies included gingival tissue only 52,54–56,58 . In 10 publications, 45–49,53,56,58–60 the authors investigated the levels of only one Wnt signaling agonist or antagonist, while the remaining six included at least two 50–52,54,55,57 . The majority of the studies used paper strips to collect GCF, while a few used paper points and microcapillary pipettes.…”