Abstract
BackgroundChronic periodontitis is associated with an increased risk for systemic conditions such as cardiovascular disease, diabetes, and osteoporosis. During chronic periodontitis, endotoxin (lipopolysaccharide, LPS) produced by P. gingivalis provokes monocyte accumulation and differentiation into macrophages and increased secretion of pro-inflammatory cytokines and matrix metalloproteases (MMPs). While normal levels of MMPs are important in cellular function, increased levels of cytokines and MMPs can cause connective tissue destruction.ResultsIn the current study, we investigated the therapeutic capability of a novel semi-synthetic sulfated polysaccharide (SAGE) on the production of cytokines and MMPs by cultured human mononuclear cells and macrophages stimulated with endotoxin LPS produced by P. gingivalis, a periodontally-relevant cell culture model. Our research demonstrated SAGE inhibited the LPS induced synthesis of inflammatory mediators including TNF-α, IL-1β, PGE2, and MMP-9 in this periodontal-relevant cell culture model. In addition, TLR-2 and TLR-4 levels were also reduced with the SAGE treatment.ConclusionsThe therapeutic potential of this novel semi-synthetic sulfated polysaccharide compound may help to prevent tissue damage and bone loss in patients with periodontal disease or other inflammatory diseases.
Highlights
Chronic periodontitis is associated with an increased risk for systemic conditions such as cardiovascular disease, diabetes, and osteoporosis
synthetic glycosaminoglycan ethers (SAGEs) is synthesized from sulfating and alkylation of nonanimal derived hyaluronic acid (HA), an immunoneutral skin polysaccharide consisting of long polymers of the disaccharide N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcA) linked GlcNacb1-3GlcAb1–4 in repeating units along the chain
Since chronic inflammatory condition such as periodontitis is characterized by a local accumulation of leukocytes, predominantly (70%) mononuclear cells, in the present study, we investigated the effect of a novel semi-synthetic sulfated polysaccharide (SAGE) on the production of cytokines and matrix metalloproteases (MMPs) by cultured human mononuclear cells/macrophages stimulated with endotoxin produced by P. gingivalis, a periodontally-relevant cell culture model
Summary
Chronic periodontitis is associated with an increased risk for systemic conditions such as cardiovascular disease, diabetes, and osteoporosis. TLR-4 is most well-known for recognizing LPS during periodontal inflammation, and play a fundamental role in pathogen recognition and activation of innate immunity via stimulation of NF-κB [3] This results in local accumulation of inflammatory cells such as neutrophils and monocytes/ macrophages and generate elevated levels of cytokines and other proinflammatory mediators such as the prostaglandins. These mediators exert autocrine or paracrine activities by upregulating the expression of matrix metalloproteinase (MMP) expression and in turn its activity contributes to the destruction and loss of periodontal connective tissue [4]. A representative SAGE structure is illustrated in (Fig. 1) which was produced from 53 kDa HA and had a final molecular weight of 5.5 kDa
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
