Vital role for osteoclasts in rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by joint inflammation and progressive joint damage — a major cause of the progressive disability characteristic of RA patients. However, despite the prevalence of the disease the molecular mechanisms involved in joint destruction have been poorly understood. In November 15 Journal of Clinical Investigation, Kurt Redlich and colleagues at the University of Vienna, Austria, show that TNF-α dependent bone destruction is mediated by osteoclasts, and that the absence of osteoclasts alters TNF-α -mediated arthritis from a destructive to a nondestructive arthritis (Journal of Clinical Investigation, 110:1419-1427, November 15, 2002).

Redlich et al. crossed transgenic mice that express human TNF (hTNFtg) and develop destructive arthritis with osteopetrotic, c-fos–deficient mice (c-fos^-/-) which completely lack osteoclasts. They observed that resulting mutant mice (c-fos^-/-hTNFtg) developed similar arthritic synovial inflammation as hTNFtg mice, but did not developed joint damage and arthritic erosions in the absence of osteoclasts.

"These findings have ...