title: Daidzein prevents the increase in CD4+CD28null T cells and B lymphopoesis in ovariectomized mice: a key mechanism for anti-osteoclastogenic effect.
abstract: Estrogen deficiency leads to an upregulation of TNF-α producing T cells and B-lymphopoesis which augments osteoclastogenesis. Estrogen deficiency also increases the population of premature senescent CD4⁺ CD28null T cells which secrete a higher amount of TNF-α thus leading to enhanced osteoclastogenesis. Isoflavonoids like daidzein and genistein are found mostly in soybeans, legumes, and peas. These share structural similarity with 17β-stradiol (E2) and have osteoprotective role. This study explores the effect of daidzein (Daid) on the proliferation of TNF-α producing T cells, premature senescent T cells and B cell lymphopoesis under estrogen deficient conditions. For this study adult Balb/c mice were treated with Daid at 10 mg/kg body weight dose by oral gavage daily post ovariectomy (Ovx). After six weeks animals were autopsied and bone marrow and spleen cells were collected for FACS analysis. Blood serum was collected for ELISA. It was observed that Ovx mice treated with Daid for six weeks show reduction in Ovx induced expansion of CD4⁺ T cells in bone marrow and spleen when analysed by flow cytometry. Estrogen deficiency led to increased prevalence of TNF-α secreting CD4⁺CD28null T cells, however, treatment with Daid increased the percentage of CD4⁺CD28⁺ T cells. Co-culture of CD4⁺CD28null T cells and bone marrow resulted in enhanced osteoclastogenesis as evident by increased tartarate resistant acid phosphatase (TRAP) expression, an osteoclast marker. However, treatment with Daid resulted in reduced osteoclastogenesis in CD4⁺CD28null T cells and bone marrow cell co-culture. Daid also regulated B lymphopoesis and decreased mRNA levels of RANKL in B220⁺ cells. Taken together, we propose that one of the mechanisms by which Daid prevents bone loss is by reversing the detrimental immune changes as a result of estrogen deficiency.
authors: Division of Endocrinology, Central Drug Research Institute (Council of Scientific and Industrial Research), Chattar Manzil, Lucknow, India.
authors: Abdul Malik
authors: AM
authors: Tyagi
authors: Kamini
authors: K
authors: Srivastava
authors: Kunal
authors: K
authors: Sharan
authors: Dinesh
authors: D
authors: Yadav
authors: Rakesh
authors: R
authors: Maurya
authors: Divya
authors: D
authors: Singh
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D018106:CD28 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D018655:Lymphocyte Count; D038041:Lymphopoiesis / Q000187:drug effects*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D010052:Ovariectomy; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011859:Radiography; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000097796:Nucleolin
chemical_list: D018106:CD28 Antigens; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D007529:Isoflavones; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000097796:Nucleolin; C004742:daidzein