Rat NFATC1 (Nuclear factor of activated T-cells, cytoplasmic 1) ELISA Kit

Wearing titanium particle-induced osteoclastogenesis, accompanied by peri-implant osteolysis, is the main cause of long-term failure of hip prosthesis. Currently, medications used for the prevention and treatment of peri-implant osteolysis show serious side effects. Therefore, development for more effective new drugs with less side effects is extremely urgent. Vaccarin is a natural flavonoid extracted from Vaccaria segetalis, with various biological functions, including antioxidantory, anti-inflammatory, and promotion of angiogenesis. However, the putative role of vaccarin in the inhibition of titanium particle-induced osteolysis has not been reported. In this study, it was indicated that vaccarin could effectively inhibit RANKL-induced osteoclastogenesis, fusion of F-actin rings, bone resorption, and expression of osteoclast marker genes in a dose-dependent manner in vitro. Moreover, vaccarin could also inhibit RANKL-induced osteoclastogenesis via the inhibition of NF-B and MAPK (p38, ERK, and JNK) signaling pathways, and inhibit the transcription of downstream transcription factors, such as c-Fos and NFATc1. Consistent with in vitro results, this in vivo study showed that vaccarin exhibited an inhibitory effect on titanium particle-induced osteolysis by antiosteoclastogenesis. In conclusion, vaccarin could be a promising agent for preventing and treating peri-implant osteolysis.

Sinomenine (SIN) is an anti-inflammatory and antiarthritic alkaloid derived from Sinomenium acutum, and the product Zhengqing Fengtongning produced from SIN has been marketed in China for treating rheumatoid arthritis (RA). Interestingly, we recently found that SIN could significantly ameliorate bone destruction induced by breast cancer cells in mice. Micro-CT examination showed that bone loss of the trabecular bones in tumor bearing mice was markedly decreased by i.p. treatment of SIN at 150 mg/kg body weight. A mechanistic study demonstrated that SIN could suppress osteoclast formation and bone absorption induced by both MDA-MB-231 cells and MDA-MB-231 cell-conditioned medium (MDA-MB-231 CM) in preosteoclastic RAW264.7 cells. The MDA-MB-231 CM-induced osteoclast-related genes TRAP and OSCAR were obviously downregulated by SIN. In addition, mRNA expression of c-Fos and NFATc1 and nuclear translocation of c-Fos and NFATcl protein were inhibited by SIN during MDA-MB-231 CM-induced osteoclastogenesis, while NF-kappa B signaling was not impacted by SIN. More interestingly, SIN was demonstrated to decrease hIL-8 mRNA expression in cultured MDA-MB-231 cells and to inhibit hIL-8 protein expression in MDA-MB-231 cells cocultured with preosteoclastic RAW264.7 cells while simultaneously downregulating CXCR1, the ligand of IL-8 related to bone destruction, during MDA-MB-231 CM-induced osteoclastogenesis. Previously, IL-8/CXCR1 was reported to be associated with the pathogenesis and progression of RA, and SIN was observed to markedly ameliorate bone erosion of RA patients. Our current findings may extend the utilization of SIN to preventing osteoclastogenesis and bone destruction in breast cancer patients and may enable IL-8/CXCR1 to serve as new targets for both anticancer and antiarthritic drug discovery.