Glycosylation of immunoglobulin G determines osteoclast differentiation and bone loss

Nat Commun. 2015 Mar 31:6:6651. doi: 10.1038/ncomms7651.


Immunglobulin G (IgG) sialylation represents a key checkpoint that determines the engagement of pro- or anti-inflammatory Fcγ receptors (FcγR) and the direction of the immune response. Whether IgG sialylation influences osteoclast differentiation and subsequently bone architecture has not been determined yet, but may represent an important link between immune activation and bone loss. Here we demonstrate that desialylated, but not sialylated, immune complexes enhance osteoclastogenesis in vitro and in vivo. Furthermore, we find that the Fc sialylation state of random IgG and specific IgG autoantibodies determines bone architecture in patients with rheumatoid arthritis. In accordance with these findings, mice treated with the sialic acid precursor N-acetylmannosamine (ManNAc), which results in increased IgG sialylation, are less susceptible to inflammatory bone loss. Taken together, our findings provide a novel mechanism by which immune responses influence the human skeleton and an innovative treatment approach to inhibit immune-mediated bone loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / diagnostic imaging
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / metabolism
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism
  • Bone Resorption / diagnostic imaging
  • Bone Resorption / immunology*
  • Bone Resorption / metabolism
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / immunology*
  • Bone and Bones / metabolism
  • Cell Differentiation / immunology*
  • Dynamic Light Scattering
  • Female
  • Galactose / metabolism
  • Glycosylation
  • Hexosamines / pharmacology
  • Humans
  • Immunoglobulin Fc Fragments / metabolism
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / metabolism
  • Male
  • Mice
  • Middle Aged
  • N-Acetylneuraminic Acid / metabolism*
  • Osteoclasts / cytology*
  • Osteoclasts / immunology
  • Osteoclasts / metabolism
  • RNA, Messenger / metabolism*
  • Receptors, Fc / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • X-Ray Microtomography


  • Hexosamines
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • RNA, Messenger
  • Receptors, Fc
  • N-Acetylneuraminic Acid
  • Galactose
  • N-acetylmannosamine