Laboratory of Molecular Biomedicine, Institute of Bioscience, Usmanu Danfodiyo University, Sokoto, Nigeria ; Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, Sokoto, Nigeria.
Clin Interv Aging. 2013;8:1259-71. doi: 10.2147/CIA.S45943. Epub 2013 Sep 24.
Osteoporosis and other bone degenerative diseases are among the most challenging non-communicable diseases to treat. Previous works relate bone loss due to osteoporosis with oxidative stress generated by free radicals and inflammatory cytokines. Alternative therapy to hormone replacement has been an area of interest to researchers for almost three decades due to hormone therapy-associated side effects.
In this study, we investigated the effects of gamma-amino butyric acid (GABA), gamma-oryzanol (ORZ), acylated steryl glucosides (ASG), and phenolic extracts from germinated brown rice (GBR) on the expression of genes related to bone metabolism, such as bone morphogenic protein-2 (BMP-2), secreted protein acidic and rich in cysteine (SPARC), runt-related transcription factor 2 (RUNX-2), osteoblast-specific transcription factor osterix (Osx), periostin, osteoblast specific factor (Postn), collagen 1&2 (Col1&2), calcitonin receptor gene (CGRP); body weight measurement and also serum interleukin-6 (IL-6) and osteocalcin, in serum and bone. Rats were treated with GBR, ORZ, GABA, and ASG at (100 and 200 mg/kg); estrogen (0.2 mg/kg), or remifemin (10 and 20 mg/kg), compared to ovariectomized non-treated group as well as non-ovariectomized non-treated (sham) group. Enzyme-linked immunosorbent assay was used to measure the IL-6 and osteocalcin levels at week 2, 4, and 8, while the gene expression in the bone tissue was determined using the Genetic Analysis System (Beckman Coulter Inc., Brea, CA, USA).
The results indicate that groups treated with GABA (100 and 200 mg/kg) showed significant upregulation of SPARC, calcitonin receptor, and BMP-2 genes (P < 0.05), while the ORZ-treated group (100 and 200 mg/kg) revealed significant (P < 0.05) upregulation of Osx, Postn, RUNX-2, and Col1&2. Similarly, IL-6 concentration decreased, while osteocalcin levels increased significantly (P < 0.05) in the treated groups as compared to ovariectomized non-treated groups.
GABA and ORZ from GBR stimulates osteoblastogenesis by upregulation of bone formation genes, possibly via the activation of GABAB receptors and by inhibiting the activity of inflammatory cytokines and reactive oxygen species. Therefore, it could be used effectively in the management of osteoporosis.
骨质疏松症和其他骨骼退行性疾病是最难治疗的非传染性疾病之一。先前的研究表明，骨质疏松症导致的骨丢失与自由基和炎性细胞因子产生的氧化应激有关。由于激素替代疗法相关的副作用，近三十年来，替代激素疗法一直是研究人员关注的焦点。
在这项研究中，我们研究了γ-氨基丁酸（GABA）、γ-谷维素（ORZ）、酰化甾醇葡萄糖苷（ASG）和发芽糙米的酚类提取物对与骨代谢相关基因的表达的影响，如骨形态发生蛋白-2（BMP-2）、富含半胱氨酸的酸性分泌蛋白（SPARC）、成骨细胞特异性转录因子 runt 相关转录因子 2（RUNX-2）、成骨细胞特异性转录因子osterix（Osx）、骨连接蛋白（periostin）、成骨细胞特异性因子（Postn）、胶原蛋白 1&2（Col1&2）、降钙素受体基因（CGRP）；体重测量以及血清中白细胞介素-6（IL-6）和骨钙素。将大鼠用 GBR、ORZ、GABA 和 ASG（100 和 200mg/kg）；雌激素（0.2mg/kg）或瑞美芬（10 和 20mg/kg）治疗，与去卵巢未治疗组以及未去卵巢未治疗（假手术）组进行比较。使用酶联免疫吸附试验（ELISA）在第 2、4 和 8 周测量 IL-6 和骨钙素水平，同时使用遗传分析系统（贝克曼库尔特公司，加利福尼亚州布雷亚）测定骨组织中的基因表达。
结果表明，用 GABA（100 和 200mg/kg）治疗的组显示 SPARC、降钙素受体和 BMP-2 基因的显著上调（P<0.05），而用 ORZ（100 和 200mg/kg）治疗的组显示 Osx、Postn、RUNX-2 和 Col1&2 的显著上调（P<0.05）。同样，与去卵巢未治疗组相比，治疗组的 IL-6 浓度降低，而骨钙素水平显著升高（P<0.05）。
来自 GBR 的 GABA 和 ORZ 通过上调骨形成基因刺激成骨细胞生成，可能通过激活 GABAB 受体和抑制炎性细胞因子和活性氧的活性来实现。因此，它可以有效地用于骨质疏松症的管理。
