Nucleosides accelerate inflammatory osteolysis, acting as distinct innate immune activators.
J Bone Miner Res
; 26(8): 1913-25, 2011 Aug.
Article
in En
| MEDLINE
| ID: mdl-21472777
ABSTRACT
The innate immune system and its components play an important role in the pathogenesis of inflammatory bone destruction. Blockade of inflammatory cytokines does not completely arrest bone erosion, suggesting that other mediators also may be involved in osteolysis. Previously we showed that nucleosides promote osteoclastogenesis and bone-resorption activity in the presence of receptor activator for nuclear factor κB ligand (RANKL) in vitro. The studies described here further demonstrate that selected nucleosides and nucleoside analogues accelerate bone destruction in mice immunized with collagen II alone (CII) but also further enhance bone erosion in mice immunized by collagen II plus complete Freund's adjuvant (CII + CFA). Abundant osteoclasts are accumulated in destructive joints. These data indicate that nucleosides act as innate immune activators distinct from CFA, synergistically accelerating osteoclast formation and inflammatory osteolysis. The potential roles of the surface triggering receptor expressed on myeloid cells (TREM) and the intracellular inflammasome in nucleoside-enhanced osteoclastogenesis have been studied. These observations provide new insight into the pathogenesis and underlying mechanism of bone destruction in inflammatory autoimmune osteoarthritis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteolysis
/
Immunity, Innate
/
Inflammation
/
Nucleosides
Limits:
Animals
Language:
En
Journal:
J Bone Miner Res
Journal subject:
METABOLISMO
/
ORTOPEDIA
Year:
2011
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA