Medicarpin inhibits osteoclastogenesis and has nonestrogenic bone conserving effect in ovariectomized mice

Tyagi, Abdul M. ; Gautam, Abnish K. ; Kumar, Amit ; Srivastava, Kamini ; Bhargavan, Biju ; Trivedi, Ritu ; Saravanan, S. ; Yadav, Dinesk K. ; Singh, Nidhi ; Pollet, Caroline ; Brazier, Michel ; Mentaverri, Romuald ; Maurya, Rakesh ; Chattopadhyay, Naibedya ; Goel, Atul ; Singh, Divya (2010) Medicarpin inhibits osteoclastogenesis and has nonestrogenic bone conserving effect in ovariectomized mice Molecular and Cellular Endocrinology, 325 (1-2). pp. 101-109. ISSN 0303-7207

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Official URL: http://doi.org/10.1016/j.mce.2010.05.016

Related URL: http://dx.doi.org/10.1016/j.mce.2010.05.016

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-κB) signaling assessed by tumor necrosis factor alpha (TNFα)-stimulated nuclear translocation of p65 subunit of NF-κB. Medicarpin also inhibited the expression of TNFα in mouse calvarial osteoblasts. This effect was ER dependent as ICI 180,782 reversed the suppressive effect of medicarpin on TNFα mRNA levels in osteoblasts. In addition, like 17β-estradiol, presence of medicarpin inhibited TNFα-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-κB ligand (RANKL) ratio and reduced mRNA levels of osteoclast markers including tartrate-resistant acid phosphatase and RANK. OVx mice administered medicarpin (10.0 mg kg−1 day−1) orally for 30 days 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.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Anti-Resorptive; Estrogen Receptor; Selective Estrogen Receptor Modulator; Osteogenic Bone Microarchitecture.
ID Code:117945
Deposited On:07 May 2021 05:34
Last Modified:07 May 2021 05:34

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