Mutan: A mixed linkage α-[(1,3)- and (1,6)]-d-glucan from Streptococcus mutans, that induces osteoclast differentiation and promotes alveolar bone loss

Carbohydr Polym. 2016 Feb 10:137:561-569. doi: 10.1016/j.carbpol.2015.11.013. Epub 2015 Nov 10.

Abstract

Mutan is an extracellular polysaccharide of Streptococcus mutans (S. mutans) that consists of α-(1,3)-linked glucose residues in main chains and α-(1,6) bonds in side chains. In the present study, mutan was isolated from S. mutans, and its structural characteristics were determined using Fourier-transform infrared spectroscopy (FT-IR) and (13)C nuclear magnetic resonance (NMR) spectroscopy. The effects of mutan on RANKL-induced osteoclast differentiation in RAW 264.7 cells were examined. Furthermore, microCT and morphometric analyses were used to determine the contribution of mutan to alveolar bone loss in the maxilla of a rat periodontitis model. Mutan increased (more than 2-fold) RANKL-induced osteoclast differentiation in a dose-dependent manner. Mutan also enhanced the alveolar bone loss in the rat maxilla 2.3-fold. In mutan-treated rats, the bone mineral density, bone volume, trabecular number, and trabecular thickness decreased, whereas trabecular separation significantly increased. In addition, mutan and lipopolysaccharide (LPS) induced similar microarray profiles in RAW 264.7 cells. A total of 43 genes related to osteoclastogenesis were differentially expressed after either mutan or LPS treatment. Five-fold increases in the expression of several genes, including IL-1β, IL-1α, IL-6, and chemokine ligands, were observed in mutan-treated RAW 264.7 cells. These results suggest a molecular mechanism for the inflammation induced by S. mutans during the establishment of periodontal disease.

Keywords: Deuterium oxide (PubChem CID: 24602); Dimethylsulfoxide (PubChem CID: 679); Intra-cortical remodelling; Isoflurane (PubChem CID: 3763); MTT formazan (PubChem CID: 16218671); Mutan; Osteoclast differentiation, Alveolar bone loss; Potassium bromide (PubChem CID: 253877); Sodium tartarate (PubChem CID: 13355); Streptococcus mutans; Trichloroacetic acid (PubChem CID: 6421).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Bone Loss / chemically induced*
  • Animals
  • Cell Differentiation*
  • Cell Line
  • Cytokines / metabolism
  • Glucans / chemistry
  • Macrophages / cytology
  • Macrophages / drug effects
  • Male
  • Mice
  • Osteoclasts / cytology
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Polysaccharides, Bacterial / chemistry
  • Polysaccharides, Bacterial / pharmacology*
  • Polysaccharides, Bacterial / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Streptococcus mutans / chemistry*

Substances

  • Cytokines
  • Glucans
  • Polysaccharides, Bacterial