Gamma-Tocotrienol Stimulates the Proliferation, Differentiation, and Mineralization in Osteoblastic MC3T3-E1 Cells

Journal of Chemistry, Jan 2018

Gamma-tocotrienol, a major component of tocotrienol-rich fraction of palm oil, has been suggested to exhibit bone protective effects in vivo. However, the effects of γ-tocotrienol on osteoblast cells are still unclear. In this study, the effects of γ-tocotrienol on the proliferation, differentiation, and mineralization in osteoblastic MC3T3-E1 cells were investigated. Our results showed that γ-tocotrienol (2–8 μmol/L) significantly improved the cell proliferation (), but it did not affect cell cycle progression. γ-Tocotrienol significantly increased alkaline phosphatase (ALP) activity (), secretion levels of osteocalcin (OC) and osteonectin (ON), and mRNA levels of collagen type I (Col I) of MC3T3-E1 cells. Meanwhile, we found that γ-tocotrienol is promoted in differentiation MC3T3-E1 cells by upregulation of the expression of Runx2 protein. Moreover, the number of bone nodules increased over 2.5-fold in cells treated with γ-tocotrienol (2–8 μmol/L) for 24 d compared to control group. These results indicated that γ-tocotrienol at low dose levels, especially 4 μmol/L, could markedly enhance the osteoblastic function by increasing the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. Moreover, our data also indicated that Runx2 protein may be involved in these effects. Further studies are needed to determine the potential of γ-tocotrienol as an antiosteoporotic agent.

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Gamma-Tocotrienol Stimulates the Proliferation, Differentiation, and Mineralization in Osteoblastic MC3T3-E1 Cells

Gamma-Tocotrienol Stimulates the Proliferation, Differentiation, and Mineralization in Osteoblastic MC3T3-E1 Cells Weili Xu,1 Pan He,1 Shenghua He,1 Pengju Cui,1 Yaqing Mi,1 Yang Yang,1 Yang Li,2 and Shaobo Zhou3 1Department of Food Science and Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China 2Department of Central Laboratory, The First Affiliated Hospital of Harbin Medical University, Harbin 150090, China 3School of Life Science, Institute of Biomedical and Environmental Science and Technology, University of Bedfordshire, Luton LU1 3JU, UK Correspondence should be addressed to Weili Xu; moc.anis@7791uxiliew and Shaobo Zhou; [email protected] Received 11 October 2017; Accepted 6 December 2017; Published 15 January 2018 Academic Editor: Ji Kang Copyright © 2018 Weili Xu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Gamma-tocotrienol, a major component of tocotrienol-rich fraction of palm oil, has been suggested to exhibit bone protective effects in vivo. However, the effects of γ-tocotrienol on osteoblast cells are still unclear. In this study, the effects of γ-tocotrienol on the proliferation, differentiation, and mineralization in osteoblastic MC3T3-E1 cells were investigated. Our results showed that γ-tocotrienol (2–8 μmol/L) significantly improved the cell proliferation (), but it did not affect cell cycle progression. γ-Tocotrienol significantly increased alkaline phosphatase (ALP) activity (), secretion levels of osteocalcin (OC) and osteonectin (ON), and mRNA levels of collagen type I (Col I) of MC3T3-E1 cells. Meanwhile, we found that γ-tocotrienol is promoted in differentiation MC3T3-E1 cells by upregulation of the expression of Runx2 protein. Moreover, the number of bone nodules increased over 2.5-fold in cells treated with γ-tocotrienol (2–8 μmol/L) for 24 d compared to control group. These results indicated that γ-tocotrienol at low dose levels, especially 4 μmol/L, could markedly enhance the osteoblastic function by increasing the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. Moreover, our data also indicated that Runx2 protein may be involved in these effects. Further studies are needed to determine the potential of γ-tocotrienol as an antiosteoporotic agent. 1. Introduction Osteoporosis affects 1/3 of women and 1/5 of men over the age of 50 years worldwide; it affects 75% of aged population in Europe, USA, and Japan [1]; and in China alone, there are 0.21 billion of people with low bone density [2]. Osteoporosis is characterized by low bone density and deterioration of bone microarchitecture [3]. Osteoporosis causes progressive bone loss and arises from an imbalance of bone resorption and formation in the bone remodeling process. There are many factors which can cause osteoporosis such as menopause, aging, thyroid diseases, and calcium deficiency [4]. Currently, most drugs for the treatment of osteoporosis focus on improvement of bone resorption, via either reducing osteoclast number (such as bisphosphonates and estrogen) or inhibition of osteoclast activity (such as cathepsin K inhibitors). However, they have little ability to stimulate new bone synthesis [1, 5–7]. Since new bone formation depends primarily on the function of osteoblasts, the agents acting by either increasing the proliferation or inducing differentiation of the osteoblasts could enhance bone formation [8, 9]. Furthermore, the potential bone-forming agents or drugs currently available either may have serious side-effects or may not improve bone quality to reduce the susceptibility to fracture. Thus, the discovery of natural dietary compounds that promote bone formation may be able to avoid the occurrence of the adverse effects of traditional drug in humans and will be of great interest. Tocotrienols and tocopherols, two subclasses of vitamin E, are abundant in food ingredients such as palm oil, rice bran oil, barley, corn, oats, rye, and wheat [10, 11]. Each of them has four stereoisomers, respectively, namely, α-, β-, γ-, and δ-tocopherols or tocotrienols (Figure 1(a)). Tocopherols contain a saturated phytol side chain in the chroman ring. Tocotrienols differ from the tocopherols in that they contain three double bonds in the side chain [12]. In previous studies, tocotrienols have been shown to have better bone protective effects when compared to α-tocopherol in animal osteoporosis models [13–19]. Furthermore, studies also showed that tocotrienols were able to prevent and even reverse osteoporosis in estrogen deficiency, testosterone deficiency, glucocorticoid excess, and nicotine exposure [15–17, 20–23]. Previous study demonstrated that palm tocotrienol is even more effective than calcium in preventing bone loss caused by estroge (...truncated)


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Weili Xu, Pan He, Shenghua He, Pengju Cui, Yaqing Mi, Yang Yang, Yang Li, Shaobo Zhou. Gamma-Tocotrienol Stimulates the Proliferation, Differentiation, and Mineralization in Osteoblastic MC3T3-E1 Cells, Journal of Chemistry, 2018, 2018, DOI: 10.1155/2018/3805932