In addition, GPNMB/OA expression is up-regulated in bone pathologies such as osteoarthritis and during fracture repair [12], [31].
This signalling pathway has also been linked to skeletal development and bone pathologies such as OP [ 32].
The osteoid bone, bone marrow cavity and collagen structure were all well characterized for appropriate diagnosis to rule out other bone pathologies such as hyperparathyroidism, Paget's disease of bone or neoplasia.
The inherent specificity of 18 F-fluoride uptake implies that other causes of increased uptake such as the surgical procedure itself or underlying bone pathology such as spondylolisthesis or secondary spondyloarthrosis should be distinguished.
We [ 15] and others [ 16] have reported that RANKL-induced osteoclast formation may be dysregulated in several bone loss pathologies, such as periprosthetic osteolysis, rheumatoid arthritis and periodontal disease, in which cells other than osteoblasts may become the source of RANKL.
Dysregulation of TLRs expression is linked to several pathologies, such as bone disease.
These compound mutants have accentuated degenerative phenotypes, which appear at earlier generation times, and suffer additional pathologies, such as bone loss and kyphosis (Chang et al, 2004; Du et al, 2004).
It was shown in mice deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity [ 28].
In summary, the importance of PLCγ2 in osteoclasts [15], [16] and neutrophils [14], [20], in conjunction with its role in DC-mediated T cell activation here discussed, positions the molecule as a point of convergence between bone and immune systems in complex pathologies such as RA and other autoimmune diseases characterized by an interplay between bone and immune cells.
Extensive evidence suggests that the immune system exerts powerful effects on bone cells, particularly in chronic disease pathologies such as rheumatoid arthritis (RA).
Magnetic resonance imaging studies have reported significant association of specific tissue pathologies such as subchondral bone lesions, synovial thickening and knee effusion with pain [ 168- 170].
