The GCF score was greater in the SAGE treatment group compared to the control group before starting the experimental treatment protocol, but the pattern of change over time for both the groups was similar to that for the clinical measurement of pocket depth (Figure 1A). A Novel Semi-Synthetic-GlycosAminoglycan Ether (SAGE) Attenuates Local and Systemic Inflammation Associated with Periodontitis and Diabetes. Keywords: periodontitis; bone loss; matrix metalloproteinases; inflammation; semi-synthetic-sulfated polysaccharide EN periodontitis bone loss matrix metalloproteinases inflammation semi-synthetic-sulfated polysaccharide 117 129 13 05/25/22 20220301 NES 220301 Introduction Periodontal disease is a chronic inflammatory disease characterized by recurrent bacterial infection followed by immune responses derived from the host, which often advances to connective tissue breakdown and alveolar bone loss.[1] In the presence of persistent bacterial challenge, Lipopolysaccharide (LPS) and other virulence factors from bacteria induce the host immune-inflammatory response by binding to Toll-like receptors 2 (TLR-2) and 4 (TLR-4), which in turn trigger Nuclear factor-kappa B (NF- B) transcription through p38 Mitogen-activated Protein kinase signal transduction system.[2] NF- B transcription up-regulates several cellular signaling cascades such as the MAPKs and promotes the expression of pro-inflammatory cytokines such as IL-1 , TNF- , IL-6 and C-reactive protein (CRP). [Extracted from the article]