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Rocaglamide-A Potentiates Osteoblast Differentiation by Inhibiting NF-κB Signaling

  • Li, Aiguo (Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University) ;
  • Yang, Libin (Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University) ;
  • Geng, Xiaolin (Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University) ;
  • Peng, Xingmei (Department of Oncology, The Third Affiliated Hospital of Xinxiang Medical University) ;
  • Lu, Tan (Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University) ;
  • Deng, Yanjun (Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University) ;
  • Dong, Yuzheng (Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University)
  • Received : 2014.12.29
  • Accepted : 2015.09.01
  • Published : 2015.11.30

Abstract

Rheumatoid arthritis is a chronic inflammatory disease that leads to bone and cartilage erosion. The inhibition of osteoblast differentiation by the inflammatory factor TNF-${\alpha}$ is critical for the pathogenesis of rheumatoid arthritis. To modulate TNF-${\alpha}$ mediated inhibition of osteoblast differentiation is required to improve therapeutic efficacy of rheumatoid arthritis. Here, we explored the potential role of rocaglamide-A, a component of Aglaia plant, in osteoblast differentiation. Rocaglamide-A prevented TNF-${\alpha}$ mediated inhibition of osteoblast differentiation, and promoted osteoblast differentiation directly, in both C2C12 and primary mesenchymal stromal cells. Mechanistically, Rocaglamide-A inhibited the phosphorylation of NF-${\kappa}B$ component p65 protein and the accumulation of p65 in nucleus, which resulted in the diminished NF-${\kappa}B$ responsible transcriptional activity. Oppositely, overexpression of p65 reversed rocaglamide-A's protective effects on osteoblast differentiation. Collectively, rocaglamide-A protected and stimulated osteoblast differentiation via blocking NF-${\kappa}B$ pathway. It suggests that rocaglamide-A may be a good candidate to develop as therapeutic drug for rheumatoid arthritis associated bone loss diseases.

Keywords

References

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