Journal
SCIENTIFIC REPORTS
Volume 9, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41598-019-53963-z
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Funding
- Ratchadapisek Sompoch Endowment Fund (2014), Chulalongkorn University [CU-57-091-IC]
- Faculty of Dentistry, Chulalongkorn University [DRF 61019]
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Osteoporotic fracture is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Mice lacking Fc gamma receptor IIb (Fc gamma RIIB) spontaneously develop lupus-like disease or SLE at 6-month-old. The aim of this study was to investigate whether Fc gamma RIIB deletion induces osteopenia. mu CT analysis indicated that deleting Fc gamma RIIB did not affect cancellous bone microarchitecture in 3-month-old mice in which SLE had not yet developed. However, 6- and 10-month-old Fc gamma RIIB-/- males that developed an SLE-like phenotype were osteopenic and Fc gamma RIIB deletion resulted in decreased cancellous bone volume. Histomorphometry confirmed a significant decrease in cancellous bone volume in 6- and 10-month-old Fc gamma RIIB-/- males. The osteoclast number was increased without any change in osteoblast number. In vitro assays indicated that deleting Fc gamma RIIB 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, Fc gamma RIIB-/- mice had higher level of serum TNF alpha, a proinflammatory cytokine. A soluble TNF alpha receptor, etanercept, prevented cancellous bone loss in Fc gamma RIIB-/- mice. Our results indicate that Fc gamma RIIB indirectly regulates cancellous bone homeostasis following SLE development. Fc gamma RIIB deletion induces inflammatory bone loss due to increased TNF alpha-mediated bone resorption without any change in bone formation in mice with SLE-like syndrome.
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