Reduction of particle-induced osteolysis by interleukin-6 involves anti-inflammatory effect and inhibition of early osteoclast precursor differentiation.

The goal of this study was to define the anti-osteoclastogenic and/or anti-inflammatory role of IL-6 in inflammatory bone resorption using in vivo and in vitro methods. To this end, titanium particles were placed on murine calvaria, and bone resorption and osteoclast formation quantified in wild-type and IL-6(-/-) mice. In this model, calvarial bone loss and osteoclast formation were increased in titanium-treated IL-6(-/-) mice.

Exposure to receptor-activator of NFkappaB ligand renders pre-osteoclasts resistant to IFN-gamma by inducing terminal differentiation.

While it has been established that IFN-gamma is a strong activator of macrophages and a potent inhibitor of osteoclastogenesis in vitro, it is also known that this cytokine is produced in particular settings of inflammatory bone loss, such as infection and psoriatic arthritis. Because of the different kinetics between rapid IFN-gamma macrophage activation (<24 hours) and the slower receptor-activator of NFkappaB ligand (RANKL) osteoclast differentiation (7 days), we postulated that IFN-gamma would have different effects on early-stage and late-stage osteoclast precursors. In RAW264.

Mechanisms of bone resorption and new bone formation in spondyloarthropathies.

Spondyloarthropathies (SpA) share clinical features such as sacroiliitis, axial immobility, and peripheral arthropathies. They also share a strong association with human leukocyte antigen-B27, implicating T cells and antigen-presenting cells in the disease process. Inflammation seems to underlie the pathogenesis of SpA, particularly in the axial skeleton and entheses.