Daphnetin inhibits RANKL‐induced osteoclastogenesis in vitro

Abstract

Osteoporosis is a common orthopedic disease which is associated with hyper-activated osteoclastogenesis. Daphnetin is a natural coumarin derivative isolated from Genus Daphne, which possesses antiarthritis effect. However, the role of daphnetin in osteoclastogenesis has not been illustrated. This study aimed to investigate the effects of daphnetin on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in vitro. Our results showed that the osteoclast formation was significantly suppressed by daphnetin treatment in bone marrow-derived macrophages (BMMs), which was illustrated by reduced number of tartrate-resistant acid phosphatase positive multinucleated osteoclasts and decreased expression levels of tumor necrosis factor receptor-associated factors (TRAF6), c-Fos, nuclear factor of activated T cells c1, and cathepsin K. RANKL caused significant induction effects in reactive oxygen species (ROS) generation and nicotinamide adenine dinucleotide phosphate oxidase activity, whereas the induction was dramatically reduced after pretreatment with daphnetin. In addition, daphnetin prevented the RANKL-induced activation of NF-κB and Akt/GSK-3β pathways in BMMs. These findings indicated that daphnetin exhibited an inhibitory effect on RANKL-induced osteoclastogenesis in vitro. The effect of daphnetin might be mediated by inhibiting ROS signal transduction, as well as preventing the activation of NF-κB and Akt/GSK-3β signaling pathways. These findings indicated that daphnetin might be considered as a new therapeutic approach for the osteoporosis treatment.

The Coumarin Derivative 5′-Hydroxy Auraptene Suppresses Osteoclast Differentiation via Inhibiting MAPK and c-Fos/NFATc1 Pathways

“…Ectopic expression of NFATc1 in osteoclast precursor cells enhanced their osteoclastogenesis even in the absence of RANKL stimulation, and mice deficient in NFATc1 expression displayed osteopetrotic defect [35,36]. In support of our findings, coumarin derivatives including daphnetin, psoralidin, and esculetin were reported to suppress osteoclastogenesis in vitro through direct inhibition of c-Fos and NFATc1 expression [16,17,30]. Coumarin derivatives have interesting pharmacological properties, and coumarin ring system has been used as a scaffold for developing therapeutic drugs for chronic diseases [37,38].…”

“…Consistently, several naturally occurring coumarin compounds showed antiosteoclastic bone resorption effects in vitro and in vivo. ese include aesculin, psoralidin, daphnetin, bakuchiol, and esculetin [16,19,30,31]. us, coumarin derivatives can be used as promising natural pharmaceutical agents for the treatment of osteoporosis.…”

“…Interestingly, numerous coumarin derivatives demonstrated in vitro and in vivo antiresorptive effects. Natural coumarin derivatives including daphnetin, psoralen, and wedelolactone were reported to exhibit an inhibitory effect on osteoclastic bone resorption [15,16]. Furthermore, psoralidin, osthole, and aesculin were protective against bone loss in osteoporotic mouse models [17][18][19].…”

Daphnetin, a Coumarin in Genus Stellera Chamaejasme Linn: Chemistry, Bioactivity and Therapeutic Potential

“…Daphnetin (7,8‐dihydroxycoumarin), a coumarin derivative ( Figure 2), was isolated from Daphne Korean Nakai with multiple pharmacological activities including anti‐cancer, anti‐inflammatory, antioxidant, anti‐diabetes, anti‐bacterial, immunosuppressive and central nervous system protection properties [51–55] . Recently, the combined employment of daphnetin with other drugs possesses a prominent prospect for the chemotherapy of many diseases.…”

5′-hydroxy Auraptene stimulates osteoblast differentiation of bone marrow-derived mesenchymal stem cells via a BMP-dependent mechanism

“…Due to the biological activities and structure–function relationships, coumarins and their derivatives showed therapeutic potentials for multiple diseases [10–13] . In this context, several coumarin derivatives were shown to have bone anabolic effects, including imperatorin and bergapten [14], Daphnetin [15], Osthole [16], Psoralen [17]. In this report, we have studied the effect of newly extracted phytochemical coumarin derivative, 5′-hydroxy auraptene,[7-(5-Hydroxy-3,7-dimethylocta-2,6-dienyloxy)-chromen-2-one], from Lotus lalambensis Schweinf on the BMSCs differentiation into osteoblasts.…”