title: Methoxyisoflavones formononetin and isoformononetin inhibit the differentiation of Th17 cells and B-cell lymphopoesis to promote osteogenesis in estrogen-deficient bone loss conditions.
abstract: Recent studies have shown that immune system plays a major role in pathophysiology of postmenopausal osteoporosis. Previously we have shown that phytoestrogens like daidzein and medicarpin exhibit immunoprotective effects, by virtue of which they alleviate bone loss. With this background, methoxyisoflavones like formononetin (formo) and isoformononetin (isoformo) that have been studied for preventing bone loss in ovariectomized rats were tested for their immunomodulatory effects in estrogen-deficient bone loss mice model.
  
  
  
  Adult Balb/c mice (N = 8/group) were given oral dose of formo and isoformo at 10 mg/kg body weight, post ovariectomy (Ovx) daily for 6 weeks. Animals were autopsied and long bones were harvested to study bone microarchitecture. Peripheral blood mononuclear cells were isolated for fluorescence-activated cell sorting and RNA analysis. Serum was collected for enzyme-linked immunosorbent assay.
  
  
  
  It was observed that formo and isoformo treatment to Ovx mice led to significant restoration of Ovx-induced deterioration of trabecular microarchitecture. Pro-osteoclastogenic subset Th17 and B cells were decreased in formo/isoformo-treated Ovx mice in comparison with vehicle-treated Ovx group. Formo and isoformo treatment to Ovx mice also led to decreased expression of Th17 diffentiation factors and promoted T-regulatory cell differentiation. Formo was more effective in enhancing the FOXP3 expression compared with isoformo. IL-17A-induced osteoclastogenesis and inhibition of osteoblast apoptosis were also suppressed by formo and isoformo treatment, with formo having a more potent effect.
  
  
  
  Our study demonstrates the immunomodulatory activity of methoxyisoflavones, formo, and isoformo, which translate into improved skeletal parameters, thereby preventing Ovx-induced bone loss.
authors.affiliation: 1Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), Central Drug Research Institute, Lucknow, India 2Academy of Science and Innovative Research, New Delhi, India 3Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow, India.
authors.forename: Mohd N
authors.initials: MN
authors.lastname: Mansoori
authors.forename: Abdul M
authors.initials: AM
authors.lastname: Tyagi
authors.forename: Priyanka
authors.initials: P
authors.lastname: Shukla
authors.forename: Kamini
authors.initials: K
authors.lastname: Srivastava
authors.forename: Kapil
authors.initials: K
authors.lastname: Dev
authors.forename: Raju
authors.initials: R
authors.lastname: Chillara
authors.forename: Rakesh
authors.initials: R
authors.lastname: Maurya
authors.forename: Divya
authors.initials: D
authors.lastname: Singh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D038041:Lymphopoiesis / Q000187:drug effects*; D008593:Menopause / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control; D010052:Ovariectomy; D048789:Phytoestrogens / Q000494:pharmacology*; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects*
chemical_list: D007529:Isoflavones; D048789:Phytoestrogens; C007768:formononetin