| First Author | Ochi S | Year | 2007 |
| Journal | Proc Natl Acad Sci U S A | Volume | 104 |
| Issue | 27 | Pages | 11394-9 |
| PubMed ID | 17592115 | Mgi Jnum | J:122820 |
| Mgi Id | MGI:3715567 | Doi | 10.1073/pnas.0701971104 |
| Citation | Ochi S, et al. (2007) Pathological role of osteoclast costimulation in arthritis-induced bone loss. Proc Natl Acad Sci U S A 104(27):11394-11399 |
| abstractText | Abnormal T cell immune responses induce aberrant expression of inflammatory cytokines such as TNF-alpha, leading to osteoclastmediated bone erosion and osteoporosis in autoimmune arthritis. However, the mechanism underlying enhanced osteoclastogenesis in arthritis is not completely understood. Here we show that TNF-alpha contributes to inflammatory bone loss by enhancing the osteoclastogenic potential of osteoclast precursor cells through inducing paired Ig-like receptor-A (PIR-A), a costimulatory receptor for receptor activator of NF-kappaB (RANK). In fact, bone erosion and osteoporosis, but not inflammation, caused by aberrant TNF-alpha expression were ameliorated in mice deficient in Fc receptor common gamma subunit or beta(2)-microglobulin, in which the expression of PIR-As and PIR-A ligands is impaired, respectively. These results establish the pathological role of costimulatory receptors for RANK in bone loss in arthritis and may provide a molecular basis for the future therapy of inflammatory diseases. |
