Fig. (4) A model describing the mechanisms by which RANKL blockade inhibits joint inflammation and bone erosion in TNFinduced
arthritis.In the inflamed joints, the human TNF transgene stimulates RANKL and TNF production by TNF receptor expressing
accessory cells. RANKL then synergizes with exogenous TNF to boost TNF production in RANK and TNF receptor double positive OCPs.
This leads to the formation of two vicious cycles: autocrine-between OCPs; and paracrine-between OCPs and accessory cells, which stimulate
more TNF and RANKL production. TNF and RANKL trigger OCP activation and differentiation. Thus, OCPs are important effector
cells to maintain the inflammation and bone erosion in TNF-induced arthritis.