title: Puerarin stimulates proliferation and differentiation and protects against cell death in human osteoblastic MG-63 cells via ER-dependent MEK/ERK and PI3K/Akt activation.
abstract: Puerarin, the main isoflavone glycoside found in the Chinese herb radix of Pueraria lobata (Willd.) Ohwi, has received increasing attention because of its possible role in the prevention of osteoporosis. Previously, we showed that puerarin could inhibit the bone absorption of osteoclasts and promote 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 not been well defined. Here we show that puerarin increases proliferation and differentiation and opposes cisplatin-induced apoptosis in human osteoblastic MG-63 cells containing two estrogen receptor (ER) isoforms. Puerarin promotes proliferation by altering cell cycle distribution whereas puerarin-mediated survival may be associated with up-regulation of Bcl-xL expression. Treatment with the ER antagonist ICI 182,780 abolishes the above actions of puerarin on osteoblast-derived cells. Using small interfering double-stranded RNA technology, we further demonstrate that the effects of puerarin on proliferation, differentiation and survival are mediated by both ERα and ERβ. Moreover, we also demonstrate that puerarin functions at least partially through activation of MEK/ERK and PI3K/Akt signaling. This agent also shows much weaker effect on breast epithelial cell growth than that of estrogen. Therefore, puerarin will be a promising agent that prevents or retards osteoporosis.
authors: Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin, People's China. wy68wy68@yahoo.com.cn
authors: Yue
authors: Y
authors: Wang
authors: Wen Liang
authors: WL
authors: Wang
authors: Wen Li
authors: WL
authors: Xie
authors: Ling Zhi
authors: LZ
authors: Li
authors: Jing
authors: J
authors: Sun
authors: Wei Jia
authors: WJ
authors: Sun
authors: Hai Ying
authors: HY
authors: Gong
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007529:Isoflavones; D011960:Receptors, Estrogen; D014665:Vasodilator Agents; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000469:Alkaline Phosphatase; C033607:puerarin
keywords: Differentiation; Osteoblast; Proliferation; Puerarin; Survival