title: Curcumin protects against ovariectomy-induced bone loss and decreases osteoclastogenesis.
abstract: Curcumin has anti-oxidative activity. In view of the increasing evidence for a biochemical link between increased oxidative stress and reduced bone density we hypothesized that curcumin might increase bone density by elevating antioxidant activity in some target cell type. We measured bone density by Micro-CT, enzyme expression levels by quantitative PCR or enzyme activity, and osteoclast (OC) formation by tartrate-resistant acid phosphatase staining. The bone mineral density of the femurs of curcumin-administered mice was significantly higher than that of vehicle-treated mice after ovariectomy (OVX) and this was accompanied by reduced amounts of serum collagen-type I fragments, which are markers of bone resorption. Curcumin suppressed OC formation by increasing receptor activator of nuclear factor-κB ligand (RANKL)-induced glutathione peroxidase-1, and reversed the stimulatory effect of homocysteine, a known H(2) O(2) generator, on OC formation by restoring Gpx activity. Curcumin generated an aberrant RANKL signal characterized by reduced expression of nuclear factor of activated T cells 2 (NFAT2) and attenuated activation of mitogen-activated protein kinases (ERK, JNK, and p38). Curcumin thus inhibited OVX-induced bone loss, at least in part by reducing osteoclastogenesis as a result of increased antioxidant activity and impaired RANKL signaling. These findings suggest that bone loss associated with estrogen deficiency could be attenuated by curcumin administration.
authors: Department of Biological Sciences (BK21 Program), University of Ulsan, Ulsan 680-749, Korea.
authors: W K
authors: WK
authors: Kim
authors: K
authors: K
authors: Ke
authors: O J
authors: OJ
authors: Sul
authors: H J
authors: HJ
authors: Kim
authors: S H
authors: SH
authors: Kim
authors: M H
authors: MH
authors: Lee
authors: H J
authors: HJ
authors: Kim
authors: S Y
authors: SY
authors: Kim
authors: H T
authors: HT
authors: Chung
authors: H S
authors: HS
authors: Choi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control*; D010052:Ovariectomy / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction; D000094765:Glutathione Peroxidase GPX1
chemical_list: D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D005979:Glutathione Peroxidase; D003474:Curcumin; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse