Dehydrocostus lactone attenuates osteoclastogenesis and osteoclast‐induced bone loss by modulating NF‐κB signalling pathway

Abstract

Osteolysis is characterized by overactivated osteoclast formation and potent bone resorption. It is enhanced in many osteoclast‐related diseases including osteoporosis and periprosthetic osteolysis. The shortage of effective treatments for these pathological processes emphasizes the importance of screening and identifying potential regimens that could attenuate the formation and function of osteoclasts. Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone containing anti‐inflammatory properties. Here, we showed that DHE suppressed receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclast formation and osteoclast marker gene expression. It also inhibited F‐actin ring formation and bone resorption in a dose‐dependent manner in vitro. Moreover, DHE inhibited the RANKL‐induced phosphorylation of NF‐κB, mitigated bone erosion in vivo in lipopolysaccharide‐induced inflammatory bone loss model and particle‐induced calvarial osteolysis model. Together, these results suggest that DHE reduces osteoclast‐related bone loss via the modulation of NF‐κB activation during osteoclastogenesis indicating that it might be a useful treatment for osteoclast‐related skeletal disorders.

Dehydrocostus Lactone Attenuates the Senescence of Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration via Inhibition of STING-TBK1/NF-κB and MAPK Signaling

“…Finally, the downstream reaction, including catabolic enzymes and inflammatory cytokines, is upregulated. A previous study reported that DHE significantly inhibited RANKL-induced osteoclast formation via the NF-κB pathway (Hu et al, 2019). Our study demonstrated similar results-that DHE significantly inhibited the phosphorylation of IKKα, IκBα, and p65 and blocked the degradation of IκBα in TNF-α-induced NP cells.…”

“…All surgical procedures were performed under general anesthesia using 3% isoflurane, were approved by the Institutional Animal Care and Ethics Committee of Ninth People's Hospital, Shanghai Jiaotong University School of Medicine (Shanghai, China), and were performed in accordance with the principles and procedures of the National Institutes of Health Guide for the Care and Use of Laboratory Animals and the Guidelines for Animal Treatment of Shanghai Jiaotong University. After the model was established, the mice were given DHE (20 mg/kg, 120 µl), according to previous research (Wang J. et al, 2017;Hu et al, 2019), or PBS (120 µl) once a day through intraperitoneal injection. Eight weeks after surgery, mice were sacrificed by surgical dislocation, and the lumbar spinal tissues were harvested and fixed in 4% PFA for subsequent downstream analyses.…”

“…Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone isolated from medicinal plants that has antioxidant, anti-inflammatory, antiulcer, and anti-hepatotoxic abilities. Previous studies have reported that DHE significantly suppressed lipopolysaccharide-induced acute lung injury and macrophage activation and suppressed estrogen deficiency-induced osteoporosis through NF-κB and MAPK signaling pathways (Hu et al, 2019;Nie et al, 2019). In this study, we conducted an experiment based on TNF-α-induced inflammation in NP cells and investigated the anti-inflammatory and anti-senescence effects of DHE.…”

Carnosol suppresses RANKL‐induced osteoclastogenesis and attenuates titanium particles‐induced osteolysis

“…Different biomaterials in particulate form exert different types and degree of adverse effects on osteolysis (Longhofer, Chong, Strong, Wooley, & Yang, 2017). Some studies reported that all particulate biomaterials caused significant increases in membrane thickness compared with control (saline) air pouches, with the highest reaction seen in response to titanium particles (Hu et al, 2019). Longhofer et al (2017) found that there were significantly more cathepsin K‐positive osteoclast‐like cells in specimens from titanium particles.…”

The Role of NLRP3 Inflammasome in Cerebrovascular Diseases Pathology and Possible Therapeutic Targets

“…Dehydrocostus lactone also inhibited potassium outflow, which may be responsible for the potent inhibition of NLRP3 and the weak inhibition of AIM2 ( Chen, Li, et al., 2020 ). Dehydrocostus lactone is reportedly involved in regulating NF-κB pathways in acute lung injury and bone metabolic disease ( Hu et al., 2019 ; Nie et al., 2019 ). Chen et al.…”