Division of Endocrinology and Metabolism, Asan Medical Center, College of Medicine, University of Ulsan, Songpa-Gu, Seoul, Republic of Korea.
Calcif Tissue Int. 2012 May;90(5):404-10. doi: 10.1007/s00223-012-9584-7. Epub 2012 Mar 21.
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.
先前，我们已经证明，腺苷酸活化蛋白激酶（AMPK）可在体外负调控核因子-κB 受体激活配体诱导的破骨细胞形成。本研究旨在探讨 AMPK 激活剂（-）-表没食子儿茶素-3-没食子酸酯（EGCG）对去卵巢（OVX）诱导的小鼠骨丢失的影响。雌性小鼠接受 OVX 手术后，给予 EGCG 治疗 8 周。我们在手术前后每 4 周测量一次全身骨矿物质密度（BMD）。我们对胫骨进行了微计算机断层扫描（micro-CT），并对股骨进行了骨组织形态计量学检查。此外，还进行了 Western blot 分析，以检测颅骨提取物中 AMPK-α的磷酸化和总形式的水平。EGCG 可预防 OVX 诱导的体重增加。与假手术对照组不同，OVX 对照组在基线和治疗后 BMD 值均未出现显著增加。EGCG 可减轻 OVX 诱导的骨丢失。micro-CT 实验显示，与 OVX 对照组相比，EGCG 可显著增加小梁骨体积和小梁数量，并减少小梁间距。组织形态计量学分析进一步表明，EGCG 可抑制破骨细胞表面和数量。EGCG 治疗后骨中磷酸化 AMPK 的表达明显升高。我们的研究结果表明，EGCG 通过抑制破骨细胞减少 OVX 诱导的骨丢失。
