Cytokines mediate bone damage by driving the differentiation and activation of the bone-resorbing cell, the osteoclast [33], as well as playing an essential role in immune cell development and immune-regulation.
Also, by crossing IL-1-/ mice with the TNFα-transgenic model of arthritis, Zwerina and colleagues [ 92] showed that IL-1 is essential for TNFα-mediated cartilage damage and has a partial role in TNFα-mediated bone damage.
Rajakumar SA, Papp E, Grandal I, Merico D, Liu CC, Allo B, et al. RANK-RANKL mediated bone destruction in B-cell acute lymphoblastic leukemia.
The balance between osetoclast mediated bone resorption and osteoblast mediated bone deposition is the essential feature of homeostatic bone remodelling.
The reduced bone turnover suggests that both treatments have effects on inflammatory mediated bone loss.
However, cartilage is aneural and cannot be a direct source of pain, and this means that the association is possibly mediated by bone damage (as a consequence of decreased bone unloading associated with cartilage loss).
Both IL-1 and TNF are inflammatory cytokines mediating bone resorption in a variety of diseases affecting bone.
These monocyte-derived osteoclasts then mediate bone destruction.
IL-6 is a proinflammatory cytokine characterized by a range of pleiotropic activities capable of mediating cartilage and bone damage, including induction of acute phase proteins and stimulation of T and B cells, synoviocytes and osteoclasts [ 44].
Similar to destruction mediated by an earthquake, bone damage is most common and most severe in the vicinity of the (inflammatory) epicenter, whereas the effects are less severe at sites distant from the epicenter, although they can still be detected (for instance, bone density measurements in the case of bone loss).
In addition, the further elevated NOS level under fatigue loading condition suggests NO may also play a key role in mediating the repair of bone damage, such as recruitment of osteoclast precursor, because its actions include changes of the vascular permeability of the damaged area and stimulation of angiogenic activity [ 41].
