As well as promoting cartilage breakdown, the joint inflammation typical of rheumatoid arthritis (RA) decreases cartilage anabolism, a process that is reversible and potentially provides a novel therapeutic strategy, say scientists.
Dominique Baeten (University of Amsterdam, The Netherlands) and associates explain that "melanoma inhibitory activity (MIA), also known as cartilage-derived retinoic acid-sensitive protein (CD-RAP), is probably secreted exclusively by bone growth plates and articular chondrocytes."
Once secreted, MIA promotes the chondrocytic differentiation of mesenchymal stem cells and is thought to encourage the formation of cartilage extracellular matrices by differentiated chondrocytes.
As healthy cartilage is dependent on an exact balance between cartilage formation and degeneration, and MIA seems to be closely involved in the homeostasis of cartilage extracellular matrices, Baeten and team reasoned that MIA might be significant in RA, which is characterized by loss of cartilage.
To verify their hypothesis, the researchers used immunohistochemistry and quantitative polymerase chain reaction to establish how MIA production was regulated in 37 patients with RA. MIA activity was also examined in synovial fluid from 30 patients with spondyloarthritis, and in vitro in human chondrocytes.
MIA was generally produced by chondrocytes in the joints of RA patients, the authors report in the Annals of Rheumatic Diseases.
Further investigation revealed that, although levels of MIA were lower in patients with RA than in those with spondyloarthritis, concentrations of the protein were inversely correlated with the degree of joint inflammation in patients with RA but not in those with spondyloarthritis.
Consistent with this, the authors showed that pro-inflammatory cytokines, which were found in the greatest concentrations in the RA patients, actively suppressed the activity of MIA in vitro. Consequently, cartilage anabolism was suppressed.
This relationship between inflammatory cytokines and MIA activity was confirmed when the investigators demonstrated that blocking the activity of tumor necrosis factor-a or interleukin-1 in RA patients increased MIA levels.
Based on their results, the authors conclude: Cartilage damage is not per definition irreversible.
"This biological concept would fit with recent radiological data demonstrating genuine structural repair after effective treatment of RA patients."