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Nutrients 2016, 8(7), 423;

Avenanthramides Prevent Osteoblast and Osteocyte Apoptosis and Induce Osteoclast Apoptosis in Vitro in an Nrf2-Independent Manner

Department of Anatomy & Cell Biology, School of Medicine, Indiana University, Indianapolis, IN 46202, USA
Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202, USA
Department of Nutrition and Food Studies, George Mason University, Fairfax, VA 22030, USA
Think Healthy Group, LLC, Washington, DC 20001, USA
National Osteoporosis Foundation, Arlington, VA 22202, USA
Department of Medicine, Division of Endocrinology, School of Medicine, Indiana University, Indianapolis, IN 46202, USA
Authors to whom correspondence should be addressed.
Received: 23 May 2016 / Revised: 30 June 2016 / Accepted: 6 July 2016 / Published: 11 July 2016
(This article belongs to the Special Issue Health-Promoting Components of Fruits and Vegetables in Human Health)
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Oats contain unique bioactive compounds known as avenanthramides (AVAs) with antioxidant properties. AVAs might enhance the endogenous antioxidant cellular response by activation of the transcription factor Nrf2. Accumulation of reactive oxygen species plays a critical role in many chronic and degenerative diseases, including osteoporosis. In this disease, there is an imbalance between bone formation by osteoblasts and bone resorption by osteoclasts, which is accompanied by increased osteoblast/osteocyte apoptosis and decreased osteoclast apoptosis. We investigated the ability of the synthethic AVAs 2c, 2f and 2p, to 1-regulate gene expression in bone cells, 2-affect the viability of osteoblasts, osteocytes and osteoclasts, and the generation of osteoclasts from their precursors, and 3-examine the potential involvement of the transcription factor Nrf2 in these actions. All doses of AVA 2c and 1 and 5 µM dose of 2p up-regulated collagen 1A expression. Lower doses of AVAs up-regulated OPG (osteoprotegerin) in OB-6 osteoblastic cells, whereas 100 μM dose of 2f and all concentrations of 2c down-regulated RANKL gene expression in MLO-Y4 osteocytic cells. AVAs did not affect apoptosis of OB-6 osteoblastic cells or MLO-Y4 osteocytic cells; however, they prevented apoptosis induced by the DNA topoisomerase inhibitor etoposide, the glucocorticoid dexamethasone, and hydrogen peroxide. AVAs prevented apoptosis of both wild type (WT) and Nrf2 Knockout (KO) osteoblasts, demonstrating that AVAs-induced survival does not require Nrf2 expression. Further, KO osteoclast precursors produced more mature osteoclasts than WT; and KO cultures exhibited less apoptotic osteoclasts than WT cultures. Although AVAs did not affect WT osteoclasts, AVA 2p reversed the low apoptosis of KO osteoclasts. These in vitro results demonstrate that AVAs regulate, in part, the function of osteoblasts and osteocytes and prevent osteoblast/osteocyte apoptosis and increase osteoclast apoptosis; further, these regulatory actions are independent of Nrf2. View Full-Text
Keywords: avenanthramides; oxidative stress; apoptosis; gene expression; bone cells avenanthramides; oxidative stress; apoptosis; gene expression; bone cells

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Pellegrini, G.G.; Morales, C.C.; Wallace, T.C.; Plotkin, L.I.; Bellido, T. Avenanthramides Prevent Osteoblast and Osteocyte Apoptosis and Induce Osteoclast Apoptosis in Vitro in an Nrf2-Independent Manner. Nutrients 2016, 8, 423.

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