Effects of Liriopis Tuber Water Extract on RANKL-induced Osteoclast Differentiation / 체질인류학회지

Increased formation and activation of osteoclast lead to unwanted bone resorption. Several natural products which have inhibitory effects on osteoclast differentiation and function are under investigation to prevent and treat the osteoporotic bone disease. Liriopis tuber has been used in Oriental medicine for the suppression of cough, expectoration, thirst, and has been used for sthenia, diuresis, blood glucose regulation, treatment of xerostomia, and constipation. Also, recently it has been reported that Liriopsis tuber has anti-inflammatory, anti-thrombic, anti-adhesive activities. The purpose of this study was to evaluate the effects of Liriopis tuber on osteoclast differentiation and was to evaluate of its mechanism. Water extract of Liriopis tuber significantly inhibited receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophages (BMMs) in a dose dependent manner. However, water extract of Liriopis tuber did not affect cytotoxicity when compared with control. The mRNA expression of c-Fos, NFATc1, tartrate resistant-acid phosphatase (TRAP), and cathepsin K induced by RANKL was inhibited by water extract of Liriopis tuber treatment. Also, water extract of Liriopis tuber inhibited the protein expression of c-Fos and NFATc1 expression in BMMs treated with RANKL. Among the signal pathways, water extract of Liriopis tuber suppressed the phosphorylation of p38 induced by RANKL. In summary, Liriopis tuber exerted inhibitory effects on osteoclast diffentiation via suppression of c-Fos and NFATc1 which are essential gene to osteoclastogenesis. Taken together, these results suggest that Liriopis tuber may be a useful candidate in the treatment of osteoporosis without special toxicity.

Inhibitory Effects of 1',2'-Dihydrorotenone on Osteoclast Differentiation and Bone Resorption In Vitro and In Vivo / 체질인류학회지

It is important to identify therapeutic compounds with no adverse effects for use in the chemotherapy of patients with bone-related diseases. The aim of this study was to identify a new compound that inhibits osteoclast differentiation and bone resorption. Herein, we examined the effects of 1',2'-dihydrorotenone on osteoclast differentiation and bone resorption in vitro and in vivo. 1',2'-dihydrorotenone inhibited receptor activator of NF-kappaB ligand (RANKL)-induced osteoclast differentiation of cultured bone marrow macrophages (BMMs) in a dose-dependent manner. However, 1',2'-dihydrorotenone did not exert cytotoxic effect on BMMs. 1',2'-dihydrorotenone suppressed the expression of c-fos and NFATc1 as well as osteoclast-specific genes in BMMs treated with RANKL. Treatment with RANKL inhibited the expression of inhibitors of differentiation/DNA binding (Id)1, 2, and 3; however, in the presence of 1',2'-dihydrorotenone, RANKL did not suppress the expression of Id1, 2, and 3. Furthermore, 1',2'-dihydrorotenone inhibited bone resorption and considerably attenuated the erosion of trabecular bone induced by lipopolysaccharide treatment. Taken together, these results suggest that 1',2'-dihydrorotenone has the potential to be applied in therapies for bone-related diseases.

Iron chelator inducesMIP-3alpha/CCL20 in human intestinal epithelial cells: implication for triggeringmucosal adaptive immunity

A previous report by this laboratory demonstrated that bacterial iron chelator (siderophore) triggers inflammatory signals, including the production of CXC chemokine IL-8, in human intestinal epithelial cells (IECs). Microarray-based gene expression profiling revealed that iron chelator also induces macrophage inflammatory protein 3 alpha (MIP-3alpha)/ CC chemokine-ligand 20 (CCL20). As CCL20 is chemotactic for the cells involved in host adaptive immunity, this suggests that iron chelator may stimulate IECs to have the capacity to link mucosal innate and adaptive immunity. The basal medium from iron chelator deferoxamine (DFO)-treated HT-29 monolayers was as chemotactic as recombinant human CCL20 at equivalent concentrations to attract CCR6+ cells. The increase of CCL20 protein secretion appeared to correspond to that of CCL20 mRNA levels, as determined by real-time quantitative RT-PCR. The efficacy of DFO at inducing CCL20 mRNA was also observed in human PBMCs and in THP-1 cells, but not in human umbilical vein endothelial cells. Interestingly, unlike other proinflammatory cytokines, such as TNF-alpha and IL-1beta, a time-dependent experiment revealed that DFO slowly induces CCL20, suggesting a novel mechanism of action. A pharmacologic study also revealed that multiple signaling pathways are differentially involved in CCL20 production by DFO, while some of those pathways are not involved in TNF-alpha-induced CCL20 production. Collectively, these results demonstrate that, in addition to some bacterial products known to induce host adaptive immune responses, direct chelation of host iron by infected bacteria may also contribute to the initiation of host adaptive immunity in the intestinal mucosa.