Lupus-like Disease in FcγRIIB−/− Mice Induces Osteopenia

Abstract

AbstractOsteoporotic fracture is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Mice lacking Fc gamma receptor IIb (FcγRIIB) spontaneously develop lupus-like disease or SLE at 6-month-old. The aim of this study was to investigate whether FcγRIIB deletion induces osteopenia. μCT analysis indicated that deleting FcγRIIB did not affect cancellous bone microarchitecture in 3-month-old mice in which SLE had not yet developed. However, 6- and 10-month-old FcγRIIB−/− males that developed an SLE-like phenotype were osteopenic and FcγRIIB deletion resulted in decreased cancellous bone volume. Histomorphometry confirmed a significant decrease in cancellous bone volume in 6- and 10-month-old FcγRIIB−/− males. The osteoclast number was increased without any change in osteoblast number. In vitro assays indicated that deleting FcγRIIB 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, FcγRIIB−/− mice had higher level of serum TNFα, a proinflammatory cytokine. A soluble TNFα receptor, etanercept, prevented cancellous bone loss in FcγRIIB−/− mice. Our results indicate that FcγRIIB indirectly regulates cancellous bone homeostasis following SLE development. FcγRIIB deletion induces inflammatory bone loss due to increased TNFα-mediated bone resorption without any change in bone formation in mice with SLE-like syndrome.