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Puerarin enhances proliferation and osteoblastic differentiation of human bone marrow stromal cells via a nitric oxide/cyclic guanosine monophosphate signaling pathway

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Puerarin, a major active isoflavone extracted from the Traditional Chinese Medicine Radix Puerariae, has been studied for its comprehensive biological effects. However, to date, its effect on bone formation and the underlying mechanism of action have not been well investigated. The present study investigated the effect of puerarin on cell proliferation and osteoblastic maturation in cultured human bone marrow stromal cells (hBMSC) in vitro. Puerarin (2.5100 µM) increased hBMSC growth in a dosedependent manner, as indicated by an MTT assay, and stimulated osteoblastic maturation as indicated by assessment of alkaline phosphatase (ALP) activity, as well as calcium deposition into the extracellular matrix detected by alizarin red S staining. Furthermore, polymerase chain reaction analysis showed that the expression of osteoblastic markers, including Runt-related transcription factor 2/core-binding factor alpha 1, osterix and osteocalcin, were increased in hBMSCs following incubation with puerarin. Further experiments indicated that puerarin increased the nitric oxide (NO) production and cyclic guanosine monophosphate (cGMP) content in hBMSCs. The effects of puerarin were mimicked by 17βestrodiol (108 M) and were abolished in the presence of estrogen receptor antagonist ICI182780 (107 M). A NO synthase inhibitor, NxnitroLarginine methylester (6x103 M), significantly attenuated puerarininduced increases in NO production and cGMP content, in parallel with a reduction of cell proliferation and osteoblastic differentiation as well as the expression of osteoblastic markers. These results suggested that puerarin may prevent osteoporosis by exerting stimulatory effects on bone formation and the NO/cGMP pathway, which has an important role in puerarininduced hBMSC proliferation and osteoblastic differentiation.
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Document Type: Research Article

Affiliations: 1: Department of Endocrinology and Metabolism, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China 2: Baiyuan Gene Technology Co. Ltd, Lanzhou, Gansu 730000, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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