title: (-)-Epigallocathechin-3-gallate, an AMPK activator, decreases ovariectomy-induced bone loss by suppression of bone resorption.
abstract: Previously, we showed that AMP-activated protein kinase (AMPK) negatively regulates receptor activator of nuclear factor-κB ligand-induced osteoclast formation in vitro. The present study investigated the effect of (-)-epigallocathechin-3-gallate (EGCG), an AMPK activator, on ovariectomy (OVX)-induced bone loss in mice. Female mice subjected to OVX were administered EGCG for 8 weeks. We measured total-body bone mineral density (BMD) before and after the operation at an interval of 4 weeks. We performed micro-computed tomography (micro-CT) of the tibia and bone histomorphometric examination of the femur. Western blot analysis was additionally performed, to detect levels of the phosphorylated and total forms of AMPK-α in calvarial extracts. EGCG prevented OVX-induced body weight gain. The OVX control did not show a significant increase in BMD values at baseline and after treatment, unlike the sham control. EGCG attenuated OVX-induced bone loss. Micro-CT experiments revealed that EGCG induced a significant increase in trabecular bone volume and trabecular number and a decrease in trabecular spacing compared to the OVX control. Histomorphometric analyses further showed that EGCG suppressed osteoclast surface and number. Phosphorylated AMPK expression was significantly elevated in bone following EGCG treatment. Our findings collectively indicate that EGCG decreases OVX-induced bone loss via inhibition of osteoclasts.
authors.affiliation: Division of Endocrinology and Metabolism, Asan Medical Center, College of Medicine, University of Ulsan, Songpa-Gu, Seoul, Republic of Korea.
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Beom-Jun
authors.initials: BJ
authors.lastname: Kim
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Cho
authors.forename: Chan Soo
authors.initials: CS
authors.lastname: Shin
authors.forename: Sook-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Lee
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
authors.forename: Ghi Su
authors.initials: GS
authors.lastname: Kim
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Koh
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D015519:Bone Density; D001862:Bone Resorption / Q000378:metabolism* / Q000503:physiopathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D020536:Enzyme Activators / Q000494:pharmacology*; D005260:Female; D051379:Mice; D010052:Ovariectomy; D011480:Protease Inhibitors / Q000494:pharmacology*
chemical_list: D020536:Enzyme Activators; D011480:Protease Inhibitors; D002392:Catechin; C045651:epigallocatechin gallate; D055372:AMP-Activated Protein Kinases