title: Rocaglamide-A Potentiates Osteoblast Differentiation by Inhibiting NF-κB Signaling.
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-α is critical for the pathogenesis of rheumatoid arthritis. To modulate TNF-α 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-α 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-κB component p65 protein and the accumulation of p65 in nucleus, which resulted in the diminished NF-κB 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-κB pathway. It suggests that rocaglamide-A may be a good candidate to develop as therapeutic drug for rheumatoid arthritis associated bone loss diseases.
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Henan, China.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Henan, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Henan, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Geng
authors.affiliation: Department of Oncology, The Third Affiliated Hospital of Xinxiang Medical University, Henan, China.
authors.forename: Xingmei
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Henan, China.
authors.forename: Tan
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Henan, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Henan, China.
authors.forename: Yuzheng
authors.initials: Y
authors.lastname: Dong
mesh_terms: D031602:Aglaia / Q000737:chemistry; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001572:Benzofurans / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010946:Plants, Medicinal / Q000737:chemistry; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D001572:Benzofurans; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C107772:rocaglamide
keywords: NF-κB; TNF-α; osteoblast differentiation; rocaglamide-A