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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 prevents RANKL-injection-induced osteoclast activity.RANKL/vehicle and RANKL/XN were injected into the calvaria of 6-week-old male mice every day, respectively (n = 6). After 15 days, the mice were sacrificed and calvaria were stained by TRAP staining and sectioned. (A) Representative TRAP stained whole calvaria (top) and calvarial section (bottom) from normal mice, RANKL/vehicle injected mice (RANKL) and RANKL/XN injected mice (RANKL + XN). (B) Eroded surface/bone surface (ES/BS); osteoclast surface/bone surface (Oc.S/BS); osteoclast number/bone perimeter (N.Oc/B.Pm) were analyzed by OsteoMeasure Analysis system as described in Materials and Methods.
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f4: XN prevents RANKL-injection-induced osteoclast activity.RANKL/vehicle and RANKL/XN were injected into the calvaria of 6-week-old male mice every day, respectively (n = 6). After 15 days, the mice were sacrificed and calvaria were stained by TRAP staining and sectioned. (A) Representative TRAP stained whole calvaria (top) and calvarial section (bottom) from normal mice, RANKL/vehicle injected mice (RANKL) and RANKL/XN injected mice (RANKL + XN). (B) Eroded surface/bone surface (ES/BS); osteoclast surface/bone surface (Oc.S/BS); osteoclast number/bone perimeter (N.Oc/B.Pm) were analyzed by OsteoMeasure Analysis system as described in Materials and Methods.

Mentions: To further confirm the observation that XN inhibits bone resorption of osteoclast in vivo, we employed the extensively used RANKL-injection-induced bone resorption mouse model212. Our results showed that RANKL-injection dramatically induced the activity of osteoclast (Fig. 4A, middle), however administration of XN strikingly suppressed the RANKL-injection-induced osteoclast activity (Fig. 4A, right). Histomorphometric analysis (RANKL + XN versus RANKL mice) indicated that XN inhibited the RANKL-injection-induced bone resorption in vivo, including the osteoclast surface/bone surface (Oc.S/BS), eroded surface/bone surface (ES/BS), and osteoclast number/bone perimeter (N.Oc/B.Pm) (Fig. 4B).


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 prevents RANKL-injection-induced osteoclast activity.RANKL/vehicle and RANKL/XN were injected into the calvaria of 6-week-old male mice every day, respectively (n = 6). After 15 days, the mice were sacrificed and calvaria were stained by TRAP staining and sectioned. (A) Representative TRAP stained whole calvaria (top) and calvarial section (bottom) from normal mice, RANKL/vehicle injected mice (RANKL) and RANKL/XN injected mice (RANKL + XN). (B) Eroded surface/bone surface (ES/BS); osteoclast surface/bone surface (Oc.S/BS); osteoclast number/bone perimeter (N.Oc/B.Pm) were analyzed by OsteoMeasure Analysis system as described in Materials and Methods.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664947&req=5

f4: XN prevents RANKL-injection-induced osteoclast activity.RANKL/vehicle and RANKL/XN were injected into the calvaria of 6-week-old male mice every day, respectively (n = 6). After 15 days, the mice were sacrificed and calvaria were stained by TRAP staining and sectioned. (A) Representative TRAP stained whole calvaria (top) and calvarial section (bottom) from normal mice, RANKL/vehicle injected mice (RANKL) and RANKL/XN injected mice (RANKL + XN). (B) Eroded surface/bone surface (ES/BS); osteoclast surface/bone surface (Oc.S/BS); osteoclast number/bone perimeter (N.Oc/B.Pm) were analyzed by OsteoMeasure Analysis system as described in Materials and Methods.
Mentions: To further confirm the observation that XN inhibits bone resorption of osteoclast in vivo, we employed the extensively used RANKL-injection-induced bone resorption mouse model212. Our results showed that RANKL-injection dramatically induced the activity of osteoclast (Fig. 4A, middle), however administration of XN strikingly suppressed the RANKL-injection-induced osteoclast activity (Fig. 4A, right). Histomorphometric analysis (RANKL + XN versus RANKL mice) indicated that XN inhibited the RANKL-injection-induced bone resorption in vivo, including the osteoclast surface/bone surface (Oc.S/BS), eroded surface/bone surface (ES/BS), and osteoclast number/bone perimeter (N.Oc/B.Pm) (Fig. 4B).

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