Synovial fluid RANKL and matrix metalloproteinase levels in enthesitis related arthritis subtype of juvenile idiopathic arthritis.

Abstract

In chronic arthritis cartilage and bone destruction occur as a consequence of synovial inflammation. It is mainly mediated by matrix metalloproteinases and RANKL-OPG pathways. Data on synovial fluid levels of these mediators in enthesitis related arthritis subtype (ERA) of JIA are not available. MMP-1, MMP-3, TIMP, sRANKL and OPG levels were measured in synovial fluid from patients with ERA and compared with other arthritides, polyarticular (Poly) JIA, RA and osteoarthritis (OA). sRANKL was detectable in 25/41 of ERA patients, 4/16 of Poly JIA patients. Median SF sRANKL level in patients with ERA was higher as compared to OA (p < 0.001) and poly JIA (p < 0.05) but were comparable to RA. The median OPG level in ERA was lower as compared to OA (p < 0.001), comparable to RA but was higher than poly JIA (p < 0.001). sRANKL/OPG ratio was significantly higher in ERA and Poly JIA compared to OA (p < 0.0001, p < 0.0001 respectively). The median MMP3 levels in ERA (74 microg/ml) was lower as compared to poly JIA (410 microg/ml; p < 0.0001) and RA (340 ug/ml; p < 0.0001) but was comparable to OA (107 microg/ml). The median level of ProMMP1 in ERA (0.70 microg/ml) was lower as compared to RA (2.9 microg/ml; p < 0.0001) and poly JIA but was elevated as compared to OA patients (0.1 microg/ml; p < 0.0001). TIMP1 levels in ERA were higher than poly JIA and RA patients. MMP3/TIMP1 ratio was lower in ERA compared to polyarticular JIA patients (p < 0.05). Ours is the first study reporting elevated sRANKL and reduced OPG levels and elevated sRANKL/OPG ratio in SF of children with JIA resulting in a mileu associated with bone loss. In addition, ERA patients had lower MMP level as well as MMP/TIMP ratio as compared to poly JIA which may partly explain lesser degree of joint damage seen in ERA as compared to poly JIA.

• Authors: Shilpi Agarwal, Ramnath Misra, Amita Aggarwal
• Journal: Rheumatology international (Rheumatol Int) Vol. 29 Issue 8 Pg. 907-11 (Jun 2009) ISSN: 1437-160X [Electronic] Germany
• PMID: 19052752 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Osteoprotegerin
• RANK Ligand
• Tissue Inhibitor of Metalloproteinase-1
• Matrix Metalloproteinases

Topics

• Adolescent
• Adult
• Aged
• Arthritis, Juvenile (classification, metabolism)
• Arthritis, Rheumatoid (metabolism)
• Child
• Child, Preschool
• Female
• Humans
• Male
• Matrix Metalloproteinases (metabolism)
• Middle Aged
• Osteoarthritis (metabolism)
• Osteoprotegerin (metabolism)
• RANK Ligand (metabolism)
• Synovial Fluid (metabolism)
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)