In this study, we investigate the mechanistic link between rheumatoid arthritis (RA) and periodontitis to identify a novel target (cathepsin K; Ctsk) for the treatment of comorbid periodontitis and RA.
MAM formation and GSK3b inactivation sustained production of the collagenase cathepsin K, a macrophage effector function closely correlated with clinical disease activity in RA and CAD.
Of note is the expression of cathepsin K in synovial fibroblasts and mononuclear macrophage-like cells at sites of cartilage erosion in RA and in interdigitating cells of lymphocyte-rich areas.
In addition, mononuclear cells expressing both TRAP and cathepsin K mRNA (preosteoclasts) were identified in bone marrow in and adjacent to areas of pannus invasion in RA erosions.
These data indicate that inhibitors of cathepsin K are effective at reducing osteoclast-mediated bone resorption and may have therapeutic potential in diseases of excessive bone resorption such as rheumatoid arthritis or osteoporosis.