Dracorhodin perchlorate inhibits osteoclastogenesis through repressing RANKL‐stimulated NFATc1 activity

Abstract

Osteolytic skeletal disorders are caused by an imbalance in the osteoclast and osteoblast function. Suppressing the differentiation and resorptive function of osteoclast is a key strategy for treating osteolytic diseases. Dracorhodin perchlorate (D.P), an active component from dragon blood resin, has been used for facilitating wound healing and anti‐cancer treatments. In this study, we determined the effect of D.P on osteoclast differentiation and function. We have found that D.P inhibited RANKL‐induced osteoclast formation and resorbed pits of hydroxyapatite‐coated plate in a dose‐dependent manner. D.P also disrupted the formation of intact actin‐rich podosome structures in mature osteoclasts and inhibited osteoclast‐specific gene and protein expressions. Further, D.P was able to suppress RANKL‐activated JNK, NF‐κB and Ca2+ signalling pathways and reduces the expression level of NFATc1 as well as the nucleus translocation of NFATc1. Overall, these results indicated a potential therapeutic effect of D.P on osteoclast‐related conditions.

Anti-Osteoclast Effect of Exportin-1 Inhibitor Eltanexor on Osteoporosis Depends on Nuclear Accumulation of IκBα–NF-κB p65 Complex

“…By binding to the receptor RANK on osteoclast precursors and stimulating intracellular TRAF6 signaling, the activation of the NF-κB and MAPK signaling pathways, which are important in the creation and differentiation of osteoclasts, is induced by RANKL ( Liu et al, 2020 ). Initiation of the NF-κB signaling cascade depends on IKK activation and IKK-mediated phosphorylation of IκBα.…”

Puerarin inhibits titanium particle‐induced osteolysis and RANKL‐induced osteoclastogenesis via suppression of the NF‐κB signaling pathway

“…Some drugs, such as dracorhodin perchlorate, were found to suppress osteoclast formation and wear particle-induced osteolysis. [30][31][32] One of these studies showed that curcumin inhibited RANKL-mediated osteoclast differentiation and promoted M2-type macrophage polarization. 33 Roato I, et al illustrated that T cells promoted osteoclastogenesis and enhanced osteoclast function in an early stage of eriprosthetic osteolysis.…”

“…In recent years, great progress has been made in the treatment of osteolytic diseases. Some drugs, such as dracorhodin perchlorate, were found to suppress osteoclast formation and wear particle‐induced osteolysis 30‐32 . One of these studies showed that curcumin inhibited RANKL‐mediated osteoclast differentiation and promoted M2‐type macrophage polarization 33 .…”

Maackiain dampens osteoclastogenesis via attenuating RANKL‐stimulated NF‐κB signalling pathway and NFATc1 activity

“…Bone marrow macrophages (BMMs), the osteoclast precursor cells, were isolated from long bones of C57BL/6J female mice and then purified as described 24 . The method was approved by University of Western Australia Animal Ethics Committee (No.…”