Heparan Sulfate Glycosaminoglycan Is Predicted to Stabilize Inflammatory Infiltrate Formation and RANKL/OPG Ratio in Severe Periodontitis in Humans

Bioengineering (Basel). 2022 Oct 18;9(10):566. doi: 10.3390/bioengineering9100566.

Abstract

Since chronically inflamed periodontal tissue exhibits extracellular matrix (ECM) degradation, the possible alternative to standard periodontitis treatment is to restore ECM by supplementing its components, including heparan sulfate glycosaminoglycan (HS GAG). Supplementation of the degraded ECM with synthetic derivatives of HS GAGs has been shown to be effective for periodontal tissue regeneration in experimental animal models of periodontitis. However, the potential of HS GAG supplementation for the treatment of periodontal disease in humans is still unknown. Here, we used a statistical model to investigate the role of HS GAG on inflammatory infiltrate formation and alveolar bone resorption in humans with severe periodontitis. The model was based on data from immunofluorescence staining (IF) of human gingiva samples, and reconstruction of a subset of HS GAG -related proteins from STRING reactome database. According to predictions, increased expression of native HS GAG might stabilize the accumulation of gingival inflammatory infiltrate (represented by the general inflammatory cell marker CD45) and alveolar bone resorption (represented by Receptor Activator of Nuclear ΚΒ ligand (RANKL) and osteoprotegerin (OPG) ratio) but could not restore them to healthy tissue levels. Therefore, supplementation of native HS GAG may be of limited benefits for the treatment of sever periodontitis in humans.

Keywords: heparan sulfate glycosaminoglycan; immunofluorescence; inflammation; periodontitis; statistical modeling.

Grants and funding

R.D. was supported by PhD students grant (University of Split, School of Medicine); D.B. was supported by the annual researcher grant (University of Zagreb); D.K. was supported by the annual researcher grant (University of Split).