Tatarinan T, an α-asarone-derived lignin, attenuates osteoclastogenesis induced by RANKL via the inhibition of NFATc1/c-Fos expression.

Abstract

We have previously reported that the lignin-like compounds, Tatarinan O (TO) and Tatarinan N (TN), extracted from the roots of Acorus tatarinowii Schott, inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. In the present study, the potential function of the α-asarone-derived lignins, Tatarinan T (TT) and Tatarinan A (TA), to regulate RANKL-induced osteoclastogenesis was investigated, and it was found that only early treatment with TT may inhibit RANKL-triggered formation of osteoclasts and resorption. The results revealed repressed expression levels of several osteoclast marker genes, including ATPase H+ -transporting V0 subunit d2 (Atp6v0d2), αvβ3 integrin, and osteoclast-associated receptor (OSCAR), following TT treatment during osteoclastogenesis. Moreover, TT reduced the expression levels of the core transcription elements, nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and c-Fos. However, western blotting analysis showed that TT treatment did not alter nuclear factor-κΒ (NF-κB) activation or mitogen-activated protein kinase (MAPK) or Syk/Btk/phospholipase Cγ2 (PLCγ2) phosphorylation. Taken together, these results suggest the potential of TT in the treatment of diseases of increased bone resorption.