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Inhibition of Osteoclastogenesis and Bone Resorption in vitro and in vivo by a prenylflavonoid xanthohumol from hops.

Li J, Zeng L, Xie J, Yue Z, Deng H, Ma X, Zheng C, Wu X, Luo J, Liu M - Sci Rep (2015)

Bottom Line: In this study, we examined the effects of xanthohumol (XN), an abundant prenylflavonoid from hops plant, on osteoclastogenesis, osteoclast resorption, and RANKL-induced signaling pathway using both in vitro and in vivo assay systems.At the molecular level, XN disrupted the association of RANK and TRAF6, resulted in the inhibition of NF-κB and Ca(2+)/NFATc1 signaling pathway during osteoclastogenesis.As a results, XN suppressed the expression of osteoclastogenesis-related marker genes, including CtsK, Nfatc1, Trap, Ctr.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Fengxian District Central Hospital and East China Normal University Joint Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

ABSTRACT
Excessive RANKL signaling leads to superfluous osteoclast formation and bone resorption, is widespread in the pathologic bone loss and destruction. Therefore, targeting RANKL or its signaling pathway has been a promising and successful strategy for this osteoclast-related diseases. In this study, we examined the effects of xanthohumol (XN), an abundant prenylflavonoid from hops plant, on osteoclastogenesis, osteoclast resorption, and RANKL-induced signaling pathway using both in vitro and in vivo assay systems. In mouse and human, XN inhibited osteoclast differentiation and osteoclast formation at the early stage. Furthermore, XN inhibited osteoclast actin-ring formation and bone resorption in a dose-dependent manner. In ovariectomized-induced bone loss mouse model and RANKL-injection-induced bone resorption model, we found that administration of XN markedly inhibited bone loss and resorption by suppressing osteoclast activity. At the molecular level, XN disrupted the association of RANK and TRAF6, resulted in the inhibition of NF-κB and Ca(2+)/NFATc1 signaling pathway during osteoclastogenesis. As a results, XN suppressed the expression of osteoclastogenesis-related marker genes, including CtsK, Nfatc1, Trap, Ctr. Therefore, our data demonstrated that XN inhibits osteoclastogenesis and bone resorption through RANK/TRAF6 signaling pathways. XN could be a promising drug candidate in the treatment of osteoclast-related diseases such as postmenopausal osteoporosis.

No MeSH data available.


Related in: MedlinePlus

XN inhibits ovariectomy-induced bone loss by inhibiting osteoclast activity in vivo.Four weeks after ovariectomy or sham-operation, mice were divided into three groups: sham-operated mice (sham), ovariectomized mice treated with vehicle (OVX) and OVX mice treated with XN (OVX + XN) (10 mg/kg, n = 6) for another five weeks. The treated mice were intraperitoneally (i.p.) injected with XN every days. Then, all the mice were euthanized for bone histomorphometry. (A,B) Histomorphometric analysis of lumbar vertebrae from sham, OVX, OVX + XN mice. Bone value/total value (BV/TV), trabecular space (Tb.Sp), and trabecular number (Tb.N) were analyzed as described in Materials and Methods. n = 6. (C,D) TRAP staining of the whole calvaria. The osteoclast area were analyzyed by OsteoMeasure Analysis system as described in Materials and Methods (D). (E) Effect of XN on mouse body weight at the concentrations tested. *p < 0.05, **p < 0.01, ***p < 0.001.
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f3: XN inhibits ovariectomy-induced bone loss by inhibiting osteoclast activity in vivo.Four weeks after ovariectomy or sham-operation, mice were divided into three groups: sham-operated mice (sham), ovariectomized mice treated with vehicle (OVX) and OVX mice treated with XN (OVX + XN) (10 mg/kg, n = 6) for another five weeks. The treated mice were intraperitoneally (i.p.) injected with XN every days. Then, all the mice were euthanized for bone histomorphometry. (A,B) Histomorphometric analysis of lumbar vertebrae from sham, OVX, OVX + XN mice. Bone value/total value (BV/TV), trabecular space (Tb.Sp), and trabecular number (Tb.N) were analyzed as described in Materials and Methods. n = 6. (C,D) TRAP staining of the whole calvaria. The osteoclast area were analyzyed by OsteoMeasure Analysis system as described in Materials and Methods (D). (E) Effect of XN on mouse body weight at the concentrations tested. *p < 0.05, **p < 0.01, ***p < 0.001.

Mentions: To further test the possible efficacy in the treatment of pathological bone loss, we examined the effect of XN in post-ovariectomy osteoporosis using a therapeutic experimental protocol. Administration of XN started four weeks after ovariectomy (OVX) and treated for five weeks (Fig. 3A). Histomorphometric analysis of lumbar vertebrae showed that the trabecular bone volume (BV/TV) and trabecular number (Tb.N) were significantly increased in XN treated mice compared to vehicle-treated OVX mice, while trabecular separation (Tb.Sp) was decreased relative to vehicle-treated OVX mice (Fig. 3B, right), suggesting that treatment of XN significantly inhibited the ovariectomy-induced bone loss. To explore whether XN suppressed bone loss through the inhibition of osteoclastogenic activity in vivo, we performed TRAP staining on the calvaria bone and quantified the TRAP positive area by software. Our data showed that treatment of OVX mice by XN dramatically decreased the OVX-induced osteoclast activity (Fig. 3C,D), indicating that XN could inhibit ovariectomy-induced osteoclast activity in vivo. Moreover, XN had little effect on body weight at the concentrations tested (Fig. 3E), suggesting little toxicity of XN at the tested doses in vivo.


Inhibition of Osteoclastogenesis and Bone Resorption in vitro and in vivo by a prenylflavonoid xanthohumol from hops.

Li J, Zeng L, Xie J, Yue Z, Deng H, Ma X, Zheng C, Wu X, Luo J, Liu M - Sci Rep (2015)

XN inhibits ovariectomy-induced bone loss by inhibiting osteoclast activity in vivo.Four weeks after ovariectomy or sham-operation, mice were divided into three groups: sham-operated mice (sham), ovariectomized mice treated with vehicle (OVX) and OVX mice treated with XN (OVX + XN) (10 mg/kg, n = 6) for another five weeks. The treated mice were intraperitoneally (i.p.) injected with XN every days. Then, all the mice were euthanized for bone histomorphometry. (A,B) Histomorphometric analysis of lumbar vertebrae from sham, OVX, OVX + XN mice. Bone value/total value (BV/TV), trabecular space (Tb.Sp), and trabecular number (Tb.N) were analyzed as described in Materials and Methods. n = 6. (C,D) TRAP staining of the whole calvaria. The osteoclast area were analyzyed by OsteoMeasure Analysis system as described in Materials and Methods (D). (E) Effect of XN on mouse body weight at the concentrations tested. *p < 0.05, **p < 0.01, ***p < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4664947&req=5

f3: XN inhibits ovariectomy-induced bone loss by inhibiting osteoclast activity in vivo.Four weeks after ovariectomy or sham-operation, mice were divided into three groups: sham-operated mice (sham), ovariectomized mice treated with vehicle (OVX) and OVX mice treated with XN (OVX + XN) (10 mg/kg, n = 6) for another five weeks. The treated mice were intraperitoneally (i.p.) injected with XN every days. Then, all the mice were euthanized for bone histomorphometry. (A,B) Histomorphometric analysis of lumbar vertebrae from sham, OVX, OVX + XN mice. Bone value/total value (BV/TV), trabecular space (Tb.Sp), and trabecular number (Tb.N) were analyzed as described in Materials and Methods. n = 6. (C,D) TRAP staining of the whole calvaria. The osteoclast area were analyzyed by OsteoMeasure Analysis system as described in Materials and Methods (D). (E) Effect of XN on mouse body weight at the concentrations tested. *p < 0.05, **p < 0.01, ***p < 0.001.
Mentions: To further test the possible efficacy in the treatment of pathological bone loss, we examined the effect of XN in post-ovariectomy osteoporosis using a therapeutic experimental protocol. Administration of XN started four weeks after ovariectomy (OVX) and treated for five weeks (Fig. 3A). Histomorphometric analysis of lumbar vertebrae showed that the trabecular bone volume (BV/TV) and trabecular number (Tb.N) were significantly increased in XN treated mice compared to vehicle-treated OVX mice, while trabecular separation (Tb.Sp) was decreased relative to vehicle-treated OVX mice (Fig. 3B, right), suggesting that treatment of XN significantly inhibited the ovariectomy-induced bone loss. To explore whether XN suppressed bone loss through the inhibition of osteoclastogenic activity in vivo, we performed TRAP staining on the calvaria bone and quantified the TRAP positive area by software. Our data showed that treatment of OVX mice by XN dramatically decreased the OVX-induced osteoclast activity (Fig. 3C,D), indicating that XN could inhibit ovariectomy-induced osteoclast activity in vivo. Moreover, XN had little effect on body weight at the concentrations tested (Fig. 3E), suggesting little toxicity of XN at the tested doses in vivo.

Bottom Line: In this study, we examined the effects of xanthohumol (XN), an abundant prenylflavonoid from hops plant, on osteoclastogenesis, osteoclast resorption, and RANKL-induced signaling pathway using both in vitro and in vivo assay systems.At the molecular level, XN disrupted the association of RANK and TRAF6, resulted in the inhibition of NF-κB and Ca(2+)/NFATc1 signaling pathway during osteoclastogenesis.As a results, XN suppressed the expression of osteoclastogenesis-related marker genes, including CtsK, Nfatc1, Trap, Ctr.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Fengxian District Central Hospital and East China Normal University Joint Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

ABSTRACT
Excessive RANKL signaling leads to superfluous osteoclast formation and bone resorption, is widespread in the pathologic bone loss and destruction. Therefore, targeting RANKL or its signaling pathway has been a promising and successful strategy for this osteoclast-related diseases. In this study, we examined the effects of xanthohumol (XN), an abundant prenylflavonoid from hops plant, on osteoclastogenesis, osteoclast resorption, and RANKL-induced signaling pathway using both in vitro and in vivo assay systems. In mouse and human, XN inhibited osteoclast differentiation and osteoclast formation at the early stage. Furthermore, XN inhibited osteoclast actin-ring formation and bone resorption in a dose-dependent manner. In ovariectomized-induced bone loss mouse model and RANKL-injection-induced bone resorption model, we found that administration of XN markedly inhibited bone loss and resorption by suppressing osteoclast activity. At the molecular level, XN disrupted the association of RANK and TRAF6, resulted in the inhibition of NF-κB and Ca(2+)/NFATc1 signaling pathway during osteoclastogenesis. As a results, XN suppressed the expression of osteoclastogenesis-related marker genes, including CtsK, Nfatc1, Trap, Ctr. Therefore, our data demonstrated that XN inhibits osteoclastogenesis and bone resorption through RANK/TRAF6 signaling pathways. XN could be a promising drug candidate in the treatment of osteoclast-related diseases such as postmenopausal osteoporosis.

No MeSH data available.


Related in: MedlinePlus