| First Author | Visitchanakun P | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 17342 |
| PubMed ID | 31758072 | Mgi Jnum | J:287335 |
| Mgi Id | MGI:6405827 | Doi | 10.1038/s41598-019-53963-z |
| Citation | Visitchanakun P, et al. (2019) Lupus-like Disease in FcgammaRIIB(-/-) Mice Induces Osteopenia. Sci Rep 9(1):17342 |
| abstractText | Osteoporotic fracture is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Mice lacking Fc gamma receptor IIb (FcgammaRIIB) spontaneously develop lupus-like disease or SLE at 6-month-old. The aim of this study was to investigate whether FcgammaRIIB deletion induces osteopenia. muCT analysis indicated that deleting FcgammaRIIB did not affect cancellous bone microarchitecture in 3-month-old mice in which SLE had not yet developed. However, 6- and 10-month-old FcgammaRIIB(-/-) males that developed an SLE-like phenotype were osteopenic and FcgammaRIIB deletion resulted in decreased cancellous bone volume. Histomorphometry confirmed a significant decrease in cancellous bone volume in 6- and 10-month-old FcgammaRIIB(-/-) males. The osteoclast number was increased without any change in osteoblast number. In vitro assays indicated that deleting FcgammaRIIB increased osteoclast differentiation while alkaline phosphatase activity and mineralization were unaltered. These changes were associated with increases in steady-state mRNA levels for the osteoclast marker genes Trap and Ctsk. Moreover, FcgammaRIIB(-/-) mice had higher level of serum TNFalpha, a proinflammatory cytokine. A soluble TNFalpha receptor, etanercept, prevented cancellous bone loss in FcgammaRIIB(-/-) mice. Our results indicate that FcgammaRIIB indirectly regulates cancellous bone homeostasis following SLE development. FcgammaRIIB deletion induces inflammatory bone loss due to increased TNFalpha-mediated bone resorption without any change in bone formation in mice with SLE-like syndrome. |
