Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats

Abnish K. Gautam, Biju Bhargavan, Abdul M. Tyagi, Kamini Srivastava, Dinesh K. Yadav, Manmeet Kumar, Akanksha Singh, Jay S. Mishra, Amar Bahadur Singh, Sabyasachi Sanyal, Rakesh Maurya, Lakshmi Manickavasagam, Sheelendra P. Singh, Wahajuddin Wahajuddin, Girish K. Jain, Naibedya Chattopadhyay, Divya Singh

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52 Scopus citations

Abstract

Dietary soy isoflavones including genistein and daidzein have been shown to have favorable effects during estrogen deficiency in experimental animals and humans. We have evaluated osteogenic effect of cladrin and formononetin, two structurally related methoxydaidzeins found in soy food and other natural sources. Cladrin, at as low as 10 nM, maximally stimulated both osteoblast proliferation and differentiation by activating MEK-Erk pathway. On the other hand, formononetin maximally stimulated osteoblast differentiation at 100 nM that involved p38 MAPK pathway but had no effect on osteoblast proliferation. Unlike daidzein, these two compounds neither activated estrogen receptor in osteoblast nor had any effect on osteoclast differentiation. Daily oral administration of each of these compounds at 10.0 mg kg-1 day-1 dose to recently weaned female Sprague-Dawley rats for 30 consecutive days, increased bone mineral density at various anatomic positions studied. By dynamic histomorphometry of bone, we observed that rats treated with cladrin exhibited increased mineral apposition and bone formation rates compared with control, while formononetin had no effect. Cladrin had much better plasma bioavailability compared with formononetin. None of these compounds exhibited estrogen agonistic effect in uteri. Our data suggest that cladrin is more potent among the two in promoting parameters of peak bone mass achievement, which could be attributed to its stimulatory effect on osteoblast proliferation and better bioavailability. To the best of our knowledge, this is the first attempt to elucidate structure-activity relationship between the methoxylated forms of daidzein and their osteogenic effects.

Original languageEnglish (US)
Pages (from-to)318-327
Number of pages10
JournalJournal of Nutritional Biochemistry
Volume22
Issue number4
DOIs
StatePublished - Apr 1 2011

Keywords

  • Differentiation
  • MAPK signaling
  • Osteogenic
  • Peak bone mass
  • Proliferation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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  • Cite this

    Gautam, A. K., Bhargavan, B., Tyagi, A. M., Srivastava, K., Yadav, D. K., Kumar, M., Singh, A., Mishra, J. S., Singh, A. B., Sanyal, S., Maurya, R., Manickavasagam, L., Singh, S. P., Wahajuddin, W., Jain, G. K., Chattopadhyay, N., & Singh, D. (2011). Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats. Journal of Nutritional Biochemistry, 22(4), 318-327. https://doi.org/10.1016/j.jnutbio.2010.02.010