PMID- 20570709
OWN - NLM
STAT- MEDLINE
DCOM- 20101122
LR  - 20121115
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 325
IP  - 1-2
DP  - 2010 Aug 30
TI  - Medicarpin inhibits osteoclastogenesis and has nonestrogenic bone conserving 
      effect in ovariectomized mice.
PG  - 101-9
LID - 10.1016/j.mce.2010.05.016 [doi]
AB  - 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.
CI  - Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
FAU - Tyagi, Abdul M
AU  - Tyagi AM
AD  - Division of Endocrinology, Central Drug Research Institute (Council of Scientific 
      and Industrial Research), Chattar Manzil, P.O. Box 173, Lucknow, India.
FAU - Gautam, Abnish K
AU  - Gautam AK
FAU - Kumar, Amit
AU  - Kumar A
FAU - Srivastava, Kamini
AU  - Srivastava K
FAU - Bhargavan, Biju
AU  - Bhargavan B
FAU - Trivedi, Ritu
AU  - Trivedi R
FAU - Saravanan, S
AU  - Saravanan S
FAU - Yadav, Dinesk K
AU  - Yadav DK
FAU - Singh, Nidhi
AU  - Singh N
FAU - Pollet, Caroline
AU  - Pollet C
FAU - Brazier, Michel
AU  - Brazier M
FAU - Mentaverri, Romuald
AU  - Mentaverri R
FAU - Maurya, Rakesh
AU  - Maurya R
FAU - Chattopadhyay, Naibedya
AU  - Chattopadhyay N
FAU - Goel, Atul
AU  - Goel A
FAU - Singh, Divya
AU  - Singh D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100604
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Estrogens)
RN  - 0 (Pterocarpans)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 6TX086I6IG (medicarpin)
SB  - IM
MH  - Animals
MH  - Bone Density Conservation Agents/*pharmacology
MH  - Bone Marrow Cells/drug effects/physiology
MH  - Cell Culture Techniques
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Down-Regulation/drug effects
MH  - Drug Evaluation, Preclinical
MH  - Estrogens/pharmacology
MH  - Female
MH  - Mice
MH  - Osteoclasts/*drug effects/*physiology
MH  - Ovariectomy
MH  - Pterocarpans/*pharmacology
MH  - Rabbits
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/pharmacology
EDAT- 2010/06/24 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/06/24 06:00
PHST- 2010/01/29 00:00 [received]
PHST- 2010/05/24 00:00 [revised]
PHST- 2010/05/28 00:00 [accepted]
PHST- 2010/06/24 06:00 [entrez]
PHST- 2010/06/24 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - S0303-7207(10)00287-X [pii]
AID - 10.1016/j.mce.2010.05.016 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2010 Aug 30;325(1-2):101-9. doi: 10.1016/j.mce.2010.05.016. 
      Epub 2010 Jun 4.