PMID- 33320370
OWN - NLM
STAT- MEDLINE
DCOM- 20210427
LR  - 20210703
IS  - 1365-3083 (Electronic)
IS  - 0300-9475 (Print)
IS  - 0300-9475 (Linking)
VI  - 93
IP  - 5
DP  - 2021 May
TI  - Immunoglobulin G complexes without sialic acids enhance osteoclastogenesis but do 
      not affect arthritis-mediated bone loss.
PG  - e13009
LID - 10.1111/sji.13009 [doi]
LID - e13009
AB  - Immunoglobulin G (IgG) is important in clearance and recognition of previously 
      presented antigens and after activation, IgGs can interact with the Fc gamma 
      receptors (FcgammaRs) on haematopoietic cells, including bone-resorbing osteoclasts. 
      The pathogenicity of IgG, that is the ability to elicit stimulatory effects via 
      FcgammaRs, can be modulated by attachment of sugar moieties, including sialic acids. 
      Human IgGs and autoantibodies are associated with bone loss in autoimmune 
      disease. However, the impact of polyclonal murine IgG via FcgammaRs on bone loss is 
      poorly understood. Here, we investigate if heat-aggregated activated murine 
      polyclonal IgG complexes have any direct effects on murine osteoclasts and if 
      they modulate arthritis-mediated bone loss. Using cell cultures of murine 
      osteoclasts, we show that IgG complexes without sialic acids (de-IgG complexes) 
      enhance receptor activator of nuclear factor kappa-Beta ligand (RANKL)-stimulated 
      osteoclastogenesis, an effect associated with increased FcgammaRIII expression. Using 
      an in vivo model of arthritis-mediated bone loss, where IgG complexes were 
      injected into arthritic knees, no effect on the severity of arthritis or the 
      degree of arthritis-mediated bone loss was detected. Interestingly, injection of 
      de-IgG complexes into non-arthritic knees increased osteoclast formation and 
      enhanced bone erosions. Our findings show that activated de-IgG complexes have no 
      additive effect on arthritis-mediated bone loss. However, de-IgG complexes 
      potentiate murine osteoclastogenesis and enhance local bone erosion in 
      non-arthritic bones, further confirming the link between the adaptive immune 
      system and bone.
CI  - (c) 2020 The Authors. Scandinavian Journal of Immunology published by John Wiley & 
      Sons Ltd on behalf of The Scandinavian Foundation for Immunology.
FAU - Sehic, Edina
AU  - Sehic E
AD  - Department of Rheumatology and Inflammation Research, Centre for Bone and 
      Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of 
      Gothenburg, Gothenburg, Sweden.
AD  - Department of Internal Medicine and Clinical Nutrition, Centre for Bone and 
      Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of 
      Gothenburg, Gothenburg, Sweden.
FAU - Westerlund, Anna
AU  - Westerlund A
AD  - Department of Internal Medicine and Clinical Nutrition, Centre for Bone and 
      Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of 
      Gothenburg, Gothenburg, Sweden.
FAU - Lagerquist, Marie K
AU  - Lagerquist MK
AUID- ORCID: 0000-0002-9089-8605
AD  - Department of Internal Medicine and Clinical Nutrition, Centre for Bone and 
      Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of 
      Gothenburg, Gothenburg, Sweden.
FAU - Lerner, Ulf H
AU  - Lerner UH
AUID- ORCID: 0000-0002-3579-1960
AD  - Department of Internal Medicine and Clinical Nutrition, Centre for Bone and 
      Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of 
      Gothenburg, Gothenburg, Sweden.
FAU - Carlsten, Hans
AU  - Carlsten H
AUID- ORCID: 0000-0002-9321-5152
AD  - Department of Rheumatology and Inflammation Research, Centre for Bone and 
      Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of 
      Gothenburg, Gothenburg, Sweden.
FAU - Henning, Petra
AU  - Henning P
AUID- ORCID: 0000-0002-9330-6265
AD  - Department of Internal Medicine and Clinical Nutrition, Centre for Bone and 
      Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of 
      Gothenburg, Gothenburg, Sweden.
FAU - Engdahl, Cecilia
AU  - Engdahl C
AUID- ORCID: 0000-0002-8914-0178
AD  - Department of Rheumatology and Inflammation Research, Centre for Bone and 
      Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of 
      Gothenburg, Gothenburg, Sweden.
AD  - Department of Internal Medicine and Clinical Nutrition, Centre for Bone and 
      Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of 
      Gothenburg, Gothenburg, Sweden.
LA  - eng
GR  - Svenska Sallskapet for Medicinsk Forskning/
GR  - Ake Wiberg Stiftelse/
GR  - ALF-agreement 770351/Vastra Gotalandsregionen/
GR  - 2013-07370/Vetenskapsradet/
GR  - 2019-01852/Vetenskapsradet/
GR  - Stiftelsen Konung Gustaf V:s 80-arsfond/
GR  - Reumatikerforbundet/
GR  - Tore Nilsons Stiftelse for Medicinsk Forskning/
PT  - Journal Article
DEP - 20201222
PL  - England
TA  - Scand J Immunol
JT  - Scandinavian journal of immunology
JID - 0323767
RN  - 0 (Fcgr3 protein, mouse)
RN  - 0 (Immunoglobulin G)
RN  - 0 (RANK Ligand)
RN  - 0 (Receptors, IgG)
RN  - 0 (Sialic Acids)
RN  - 0 (Tnfsf11 protein, mouse)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/immunology/*pathology
MH  - Bone Resorption/immunology/*pathology
MH  - Female
MH  - Immunoglobulin G/chemistry/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Osteoclasts/cytology/metabolism
MH  - Osteogenesis/*physiology
MH  - RANK Ligand/metabolism
MH  - Receptors, IgG/chemistry/*immunology
MH  - Sialic Acids/metabolism
PMC - PMC8243958
OTO - NOTNLM
OT  - antibodies/immunoglobulins
OT  - experimental animals
OT  - fc receptors
OT  - in vitro
OT  - osteoclast
COIS- The author displays no conflict of interest.
EDAT- 2020/12/16 06:00
MHDA- 2021/04/28 06:00
PMCR- 2021/06/30
CRDT- 2020/12/15 12:16
PHST- 2020/11/16 00:00 [revised]
PHST- 2020/07/06 00:00 [received]
PHST- 2020/12/06 00:00 [accepted]
PHST- 2020/12/16 06:00 [pubmed]
PHST- 2021/04/28 06:00 [medline]
PHST- 2020/12/15 12:16 [entrez]
PHST- 2021/06/30 00:00 [pmc-release]
AID - SJI13009 [pii]
AID - 10.1111/sji.13009 [doi]
PST - ppublish
SO  - Scand J Immunol. 2021 May;93(5):e13009. doi: 10.1111/sji.13009. Epub 2020 Dec 22.