Secreted frizzled‐related protein 5 serum levels in human periodontitis—A nested case–control study

Abstract

Aim Recombinant secreted frizzled‐related protein 5 (sFRP5) improved periodontal status in mice. Thus, this study aimed to investigate this finding in human periodontitis using an epidemiological approach. Materials and Methods sFRP5 and wnt5a concentrations were determined in human serum from the Food Chain Plus cohort using ELISAs. A total of 128 patients with periodontitis and tooth loss and 245 patients with periodontitis without tooth loss were compared to 373 sex‐, smoker‐, age‐ and BMI‐matched individuals in a nested case–control design. Results Systemic sFRP5 serum levels were significantly lower in patients with periodontitis and tooth loss (2.5 [0.0–10.4] ng/ml, median [IQR]) compared to patients with periodontitis without tooth loss (6.0 [2.5–15.8] ng/ml, median [IQR], p = 0.04] and matched controls (7.0 [2.5–18.3] ng/ml, median [IQR], p = 0.02). No significant differences in sFRP5 serum levels were found among patients with periodontitis without tooth loss (6.0 [2.5–15.8] ng/ml, median [IQR]) and controls (3.1 [0.0–10.6] ng/ml, median [IQR], p = 0.06). Conclusions sFRP5 might serve as a novel biomarker for periodontitis severity. Modulating the inflammatory background of severe forms of periodontitis, in the time of precision medicine, needs to be revealed in further studies.

Wnt Signaling in Periodontal Disease

“…Also, one study reported higher SOST protein levels in tissue samples from patients with moderate to severe periodontitis, while a similar trend, albeit not statistically significant, was seen for Wnt5a (77). When using a more permissive classification of periodontitis, the difference between disease and control tissues was not observed in samples from gingival crevicular fluid, suggesting that changes in the expression of Wnt5a might be highly restricted to the damaged site in severe periodontitis, thus explaining the absence of significant differences in serum samples (75).…”

“…One report measured Wnt5a levels in serum, failing to observe differences between subjects with and without periodontitis; however, there was higher expression of sFRP5 in patients without periodontitis, relative to patients with periodontitis followed by tooth loss, leading to changes in the sFRP5/Wnt5a ratio (75). In contrast, two independent studies (44,76) correlated an increased expression of WNT5A with a higher degree of periodontal destruction and observed lower expression of this ligand in healthy subjects.…”

Role of Wnt5a in periodontal tissue development, maintenance, and periodontitis: Implications for periodontal regeneration (Review)

“…In addition, the Sfrp5/Wnt5a axis might have a role in the association between periodontitis and systemic inflammatory disorders (including obesity, type 2 diabetes, and coronary artery disease). A nested case-control study found that in overweight individuals (body mass index, 24-38 kg/m²), Sfrp5 serum levels in patients with periodontitis involving tooth loss were significantly lower than in patients with periodontitis without tooth loss and the matched control group, while Wnt5a had no significant difference (48). Obese human subjects had significantly lower serum Sfrp5 levels than lean controls, while they had significantly higher serum Wnt5a levels (49).…”

Secreted frizzled-related protein 5 (SFRP5) protects ATDC5 cells against LPS-induced inflammation and apoptosis via inhibiting Wnt5a/JNK pathway

“…The structure of SFRPs contains a netrin-like functional domain and a cysteine-rich domain, both of which are high homologous with the cysteine-rich domain of coiled protein and can compete with coiled protein to bind wingless-type family (Wnt) ligands, thus exerting a negative regulatory effect on the Wnt pathway [8]. SFRP5 has been identified as an anti-inflammatory adipokine, an endogenous inhibitor of Wnt5a signaling [8,9]. Previous studies unanimously reported that SFRP5 exerted an antiinflammatory effect by inhibiting the non-canonical Wnt5a/ c-Jun N-terminal kinase (JNK) signaling pathway, therefore playing a key role in repressing the occurrence and development of various diseases including obesity, cardiovascular diseases, and diabetes [10,11].…”