Effects of α/β-androstenediol immune regulating hormones on bone remodeling and apoptosis in osteoblasts

Urban, Nicole H.; Chamberlin, Brett; Ramage, Samuel C.; Roberts, Zachary V.; Loria, Roger M.; Beckman, Matthew J.

doi:10.1016/j.jsbmb.2008.04.005

Cited by 8 publications

(3 citation statements)

References 48 publications

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“…Those studies used the immortalized human fetal osteoblast cell line hFOB-9 [55] and showed that β-AET suppressed PPARγ activation. PPARγ is essential for adipogenesis, endocrine function of adipose tissue and stem cell fate decisions that lead to the adipogenic commitment at the expense of the osteoblastic lineage [56].…”

Section: Discussionmentioning

confidence: 99%

5-Androstene-3β,7β,17β-triol (β-AET) Slows Thermal Injury Induced Osteopenia in Mice: Relation to Aging and Osteoporosis

et al. 2010

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5-androstene-3β,7β,17β-triol (β-AET), an active metabolite of dehydroepiandrosterone (DHEA), reversed glucocorticoid (GC)-induced suppression of IL-6, IL-8 and osteoprotegerin production by human osteoblast-like MG-63 cells and promoted osteoblast differentiation of human mesenchymal stem cells (MSCs). In a murine thermal injury model that includes glucocorticoid-induced osteopenia, β-AET significantly (p<0.05) preserved bone mineral content, restored whole body bone mineral content and endochondral growth, suggesting reversal of GC-mediated decreases in chondrocyte proliferation, maturation and osteogenesis in the growth plate. In men and women, levels of β-AET decline with age, consistent with a role for β-AET relevant to diseases associated with aging. β-AET, related compounds or synthetic derivatives may be part of effective therapeutic strategies to accelerate tissue regeneration and prevent or treat diseases associated with aging such as osteoporosis.

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Section: Discussionmentioning

confidence: 99%

5-Androstene-3β,7β,17β-triol (β-AET) Slows Thermal Injury Induced Osteopenia in Mice: Relation to Aging and Osteoporosis

et al. 2010

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“…Prior studies by our group and others indicate that androgenic hormones and AED play a role in promoting bone remodeling as reported in osteoblast cells. 24,25 In this first study, the myelopoeitic recovery was incomplete 14 days postirradiation, but the restorative effect of AED is clearly evident. It may be beneficial for future experiments with AED to be carried out for longer durations.…”

mentioning

confidence: 76%

Beta Androstenediol Mitigates the Damage of 1 GeV/n Fe Ion Particle Radiation to the Hematopoietic System

Loria

Beckman

Contaifer

et al. 2011

Cancer Biotherapy and Radiopharmaceuticals

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Space exploration is associated with exposure to 1-3 Gy solar particle radiation and galactic cosmic radiation that could increase cancer rates. Effective nontoxic countermeasures to high linear energy transfer (LET) radiation exposure are highly desirable but currently not available. The aim was to determine whether a single subcutaneous injection of androstenediol (D 5 androsten-3b, 17b-diol [AED]) could mitigate and restore the mouse hematopoetic system from the radiation-mediated injury of 3 Gy whole-body high LET 56 Fe 26 + exposure. The findings show that postradiation AED treatment has an overall positive and significant beneficial effect to restore the levels of hematopoeitic elements ( p < 0.001). Androstenediol treatment significantly increased monocyte levels at days 4, 7, and 14 and, similarly, increased red blood cell, hemoglobin, and platelet counts. Flow cytometry analysis 14 days after radiation and AED treatment demonstrated an increase ( p < 0.05) in bone marrow cells counts. Ex vivo osteoclastogenesis studies show that AED treatment is necessary and advantageous for the development and restoration of osteoclastogenesis after radiation exposure. These findings clearly show that androstenediol functions as a countermeasure to remedy hematopoeitic injury mediated by high LET iron ion radiation. Presently, no other agent has been shown to have such properties.

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“…All the furanosteroids 1–6 have derived structure from 1α,2α-epoxy-3β-hydroxyandrosta-5,8-dieno[6,5,4- bc ]furan-7,17-dione and were screened for ROS inducing activity, NF-κB inhibitory, and cytotoxic activity in hormone-independent TNBC cells (7). Furanosteroids 1 – 6 displayed several different biological activities (Table I)(8, 9). Herein, the androsta-5, 8-dienofuran structure was modified and subsequently the anti-proliferative effects were examined for the obtained derivatives.…”

Section: Discussionmentioning

confidence: 99%

Differential Effect of Wortmannolone Derivatives on MDA-MB-231 Breast Cancer Cells

Acuña

Curley

Fatima

et al. 2017

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Background/Aim The survival rate of women diagnosed with triple-negative breast-cancer (TNBC) remains low. Hence, this study aimed at the chemical and biological optimization of furanosteroid derivatives for the treatment of this type of malignancy using TNBC cells. Materials and Methods Semi-synthetic analogs of wortmannolone (1–6) that negatively affected the aberrant pathways in tumor cells were evaluated in hormone-independent breast cancer cells using western blot and cell cycle analysis. Results Wortmannolone derivatization generated NF-κB inhibitors as new lead structures for further development. Compound (3) was found to be the most significantly active lead. Conclusion Structure-activity analysis in the present study showed that acetylation of the hydroxyl groups and substitution on C3 and C17 of wortmannolone enhanced biological activity. Alpha-substitution of the acetyl group in C3 on ring A (compound 3) resulted in ROS inducing effect; however, presence of an acetyl group in β-position of C3 displayed the highest NF-κB p65 inhibitory activity (0.60 μM).

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Effects of α/β-androstenediol immune regulating hormones on bone remodeling and apoptosis in osteoblasts

Cited by 8 publications

References 48 publications

5-Androstene-3β,7β,17β-triol (β-AET) Slows Thermal Injury Induced Osteopenia in Mice: Relation to Aging and Osteoporosis

5-Androstene-3β,7β,17β-triol (β-AET) Slows Thermal Injury Induced Osteopenia in Mice: Relation to Aging and Osteoporosis

Beta Androstenediol Mitigates the Damage of 1 GeV/n Fe Ion Particle Radiation to the Hematopoietic System

Differential Effect of Wortmannolone Derivatives on MDA-MB-231 Breast Cancer Cells

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