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  • Title: Medicarpin inhibits osteoclastogenesis and has nonestrogenic bone conserving effect in ovariectomized mice.
    Author: Tyagi AM, Gautam AK, Kumar A, Srivastava K, Bhargavan B, Trivedi R, Saravanan S, Yadav DK, Singh N, Pollet C, Brazier M, Mentaverri R, Maurya R, Chattopadhyay N, Goel A, Singh D.
    Journal: Mol Cell Endocrinol; 2010 Aug 30; 325(1-2):101-9. PubMed ID: 20570709.
    Abstract:
    Medicarpin, a pterocarpan class of naturally occurring benzopyran furanobenzene compound was synthesized in gram scale to investigate its effects on murine bone cells and in ovariectomized (OVx) mice. Medicarpin, at as low as 10(-10)M suppressed osteoclastogenesis in bone marrow cells (BMCs). Medicarpin-induced apoptosis of mature osteoclasts isolated from long bones. Effects of medicarpin in osteoclasts appear to be independent of estrogen receptor (ER) activation as ICI 180,782 failed to abrogate its effects on osteoclasts. In calvarial osteoblasts, medicarpin (10(-10)M) blocked nuclear factor kappaB (NF-kappaB) signaling assessed by tumor necrosis factor alpha (TNFalpha)-stimulated nuclear translocation of p65 subunit of NF-kappaB. Medicarpin also inhibited the expression of TNFalpha in mouse calvarial osteoblasts. This effect was ER dependent as ICI 180,782 reversed the suppressive effect of medicarpin on TNFalpha mRNA levels in osteoblasts. In addition, like 17beta-estradiol, presence of medicarpin inhibited TNFalpha-induced upregulation of interleukin-1, and -6 mRNA levels in osteoblasts. In co-cultures consisting of calvarial osteoblasts and BMCs, presence of medicarpin increased osteoprotegerin (OPG)/receptor activator of NF-kappaB ligand (RANKL) ratio and reduced mRNA levels of osteoclast markers including tartrate-resistant acid phosphatase and RANK. OVx mice administered medicarpin (10.0mgkg(-1)day(-1)) orally for 30days had reduced formation of osteoclasts but increased formation of osteoprogenitor cells in BMCs compared with OVx+vehicle group. Medicarpin treatment to OVx mice maintained parameters of trabecular microarchitecure. Medicarpin exhibited no uterine estrogenicity. Our findings point towards direct and indirect inhibitory effects of medicarpin on osteoclastogenesis in vitro that contribute to its bone sparing effect in OVx mice.
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