Puerarin concurrently stimulates osteoprotegerin and inhibits receptor activator of NF-κB ligand (RANKL) and interleukin-6 production in human osteoblastic MG-63 cells.
Puerarin, a daidzein-8-C-glucoside, is the major isoflavone glycoside found in the Chinese herb radix of Pueraria lobata (Willd.) Ohwi, and has received increasing attention because of its possible role in the prevention of osteoporosis. In our previous studies, puerarin reduced the bone resorption of osteoclasts and promoted long bone growth in fetal mouse in vitro. Further study confirmed that puerarin stimulated proliferation and differentiation of osteoblasts in rat. However, the mechanisms underlying its actions on human bone cells have remained largely unknown. Here we show that puerarin concurrently stimulates osteoprotegerin (OPG) and inhibits receptor activator of nuclear factor-κB ligand (RANKL) and Interleukin-6 (IL-6) production by human osteoblastic MG-63 cells containing two estrogen receptor (ER) isotypes. Treatment with the ER antagonist ICI 182,780 abrogates the above actions of puerarin on osteoblast-derived cells. Using small interfering double-stranded RNAs technology, we further demonstrate that the effects of puerarin on OPG and RANKL expression are mediated by both ERα and ERβ but those on IL-6 production primarily by ERα. Moreover, we demonstrate that puerarin may promote activation of the classic estrogen response element (ERE) pathway through increasing ERα, ERβ and steroid hormone receptor coactivator (SRC)-1 expression. Therefore, puerarin will be a promising agent that prevents or retards osteoporosis.
Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin, People's Republic of China; Department of Pathogenic Biology and Immunology, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China. Electronic address: wangyue6808@126.com.
Yue
Y
Wang
Department of Anesthesiology, Affiliated Hospital of Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
Cheng
C
Yang
Department of Pharmacology, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
Wen Li
WL
Xie
Department of Pharmacology, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
Yan Wei
YW
Zhao
Department of Pathogenic Biology and Immunology, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
Zong Min
ZM
Li
Department of Pathogenic Biology and Immunology, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
Wei Jia
WJ
Sun
Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin, People's Republic of China; Department of Pharmaceutical Chemistry, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China. Electronic address: llzhx@yahoo.cn.
Ling Zhi
LZ
Li
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000517:prevention & control*; D053244:Osteoprotegerin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029908:Pueraria / Q000737:chemistry*; D053245:RANK Ligand / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C508600:IL6 protein, human; D015850:Interleukin-6; D007529:Isoflavones; D053244:Osteoprotegerin; D053245:RANK Ligand; D034741:RNA, Small Interfering; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C033607:puerarin
Estrogen receptor; IL-6; OPG; Osteoblast; Pueraria lobata; Puerarin; RANKL