PMID- 12379632
OWN - NLM
STAT- MEDLINE
DCOM- 20021212
LR  - 20220317
IS  - 0003-4967 (Print)
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Linking)
VI  - 61 Suppl 2
IP  - Suppl 2
DP  - 2002 Nov
TI  - Bone destruction in arthritis.
PG  - ii84-6
AB  - Rheumatoid arthritis (RA) is characterised by the presence of an inflammatory 
      synovitis accompanied by destruction of joint cartilage and bone. Destruction of 
      cartilage matrix results predominantly from the action of connective tissue 
      proteinases released by RA synovial tissues, chondrocytes, and pannus tissue. 
      Several lines of evidence in RA and in animal models of arthritis support a role 
      for osteoclasts in the pathogenesis of bone erosions. RA synovial tissues produce 
      a variety of cytokines and growth factors that may increase osteoclast formation, 
      activity, and/or survival. These include interleukin 1alpha (IL1alpha) and beta, 
      tumour necrosis factor alpha (TNFalpha), IL11, IL17, and macrophage colony 
      stimulating factor (M-CSF). Receptor activator of NFkappaB ligand (RANKL) is an 
      essential factor for osteoclast differentiation and also functions to augment T 
      cell-dendritic cell cooperative interactions. CD4+ T cells and synovial 
      fibroblasts derived from RA synovium are sources of RANKL. Furthermore, in 
      collagen induced arthritis (CIA), blockade with osteoprotegerin (OPG), a decoy 
      receptor for RANKL, results in protection from bone destruction. To further 
      evaluate the role of osteoclasts in focal bone erosion in arthritis, arthritis 
      was generated in the RANKL knockout mouse using a serum transfer model. Despite 
      ongoing inflammation, the degree of bone erosion in arthritic RANKL knockout 
      mice, as assessed by microcomputed tomography and correlated histopathological 
      analysis, was dramatically reduced compared with that seen in arthritic control 
      mice. Cartilage damage was present in both the arthritic RANKL knockout mice and 
      in arthritic control littermates, with a trend toward milder cartilage damage in 
      the RANKL knockout mice. This study supports the hypothesis that osteoclasts play 
      an important part in the pathogenesis of focal bone erosion in arthritis, and 
      reveals distinct mechanisms of cartilage destruction and bone erosion in this 
      animal model of arthritis. Future directions for research in this area include 
      the further investigation of a possible direct role for the RANKL/RANK/OPG system 
      in cartilage metabolism, and the possible role of other cell types and cytokines 
      in bone erosion in arthritis.
FAU - Gravallese, E M
AU  - Gravallese EM
AD  - Department of Medicine, Beth Israel Deaconess Medical Center, New England Baptist 
      Bone and Joint Institute, Harvard Institutes of Medicine, 4 Blackfan Circle, Room 
      241, Boston, MA 02115, USA. egravall@caregroup.harvard.edu
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Carrier Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Osteoprotegerin)
RN  - 0 (RANK Ligand)
RN  - 0 (Receptor Activator of Nuclear Factor-kappa B)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (TNFRSF11A protein, human)
RN  - 0 (TNFRSF11B protein, human)
RN  - 0 (TNFSF11 protein, human)
RN  - 0 (Tnfrsf11a protein, mouse)
RN  - 0 (Tnfrsf11b protein, mouse)
RN  - 0 (Tnfsf11 protein, mouse)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/pathology
MH  - Arthritis, Rheumatoid/*complications
MH  - Carrier Proteins/physiology
MH  - Glycoproteins/physiology
MH  - Humans
MH  - Membrane Glycoproteins/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Osteoclasts/pathology
MH  - Osteoporosis/*etiology/physiopathology
MH  - Osteoprotegerin
MH  - RANK Ligand
MH  - Receptor Activator of Nuclear Factor-kappa B
MH  - Receptors, Cytoplasmic and Nuclear/physiology
MH  - Receptors, Tumor Necrosis Factor
PMC - PMC1766721
EDAT- 2002/10/16 04:00
MHDA- 2002/12/13 04:00
PMCR- 2005/11/01
CRDT- 2002/10/16 04:00
PHST- 2002/10/16 04:00 [pubmed]
PHST- 2002/12/13 04:00 [medline]
PHST- 2002/10/16 04:00 [entrez]
PHST- 2005/11/01 00:00 [pmc-release]
AID - 10.1136/ard.61.suppl_2.ii84 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2002 Nov;61 Suppl 2(Suppl 2):ii84-6. doi: 
      10.1136/ard.61.suppl_2.ii84.