title: Wogonin inhibits osteoclast differentiation by inhibiting NFATc1 translocation into the nucleus.
abstract: The aim of the present study was to identify a natural product with the ability to inhibit nuclear factor of activated T cells c1 (NFATc1) translocation from the cytoplasm to the nucleus by high-throughput screening, and to investigate the effect of the natural product upon osteoclast differentiation and its underlying mechanism. An NFATc1 antagonist redistribution assay was performed in U2OS-NFATc1 cells against a natural product library, and Wogonin was found to have the ability to inhibit the NFATc1 translocation from the cytoplasm to the nucleus. The effect of Wogonin on NFATc1 transcription activation was further determined by luciferase assay. An osteoclast differentiation assay was executed to evaluate the effect of Wogonin on osteoclast differentiation. The effect of Wogonin upon the vital genes in osteoclast differentiation was investigated using fluorescent quantitative polymerase chain reaction analysis. The natural product Wogonin significantly inhibited the translocation of NFATc1 from the cytoplasm to the nucleus and its transcriptional activation activity. Wogonin also significantly inhibited osteoclast differentiation and decreased the transcription of osteoclast-associated immunoglobulin-like receptor, tartrate-resistant acid phosphatase and calcitonin receptor. In conclusion, the natural product Wogonin inhibited osteoclast differentiation through the inhibition of NFATc1 translocation from the cytoplasm to the nucleus, and thus the downregulation of genes associated with osteoclast differentiation, which marked Wogonin as a potential treatment for osteoporosis.
authors.affiliation: Department of Orthopedic Surgery I, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Geng
authors.affiliation: Department of Orthopedic Surgery I, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Libin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Orthopedic Surgery I, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery I, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Qin
authors.affiliation: Department of Orthopedic Surgery I, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Qiudong
authors.initials: Q
authors.lastname: Liang
keywords: NFATc1; Wogonin; osteoclast; osteoporosis