School of Traditional Chinese Medicine, Capital Medical University and Beijing Key Lab of TCM Collateral Disease Theory Research, No. 10 Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.
Food Funct. 2019 Dec 11;10(12):8026-8041. doi: 10.1039/c9fo01322a.
Senile osteoporosis (SOP) is a related disease of systematic degenerative changes in bones during natural aging. Increasing age is an important factor in its pathogenesis. This experiment was to evaluate the comprehensive effect of calcium with vitamin D3 (CaD) on SOP based on multilayer perception (MLP)-artificial neural network (ANN) methods. 15-month-old male Sprague-Dawley rats were administered CaD for 2 months, while 3-, 6-, 9-, 12-, 15- and 17-month-old rats were used as the mature or aging control groups. We detected the bone mass and bone mineral density (BMD), performed biomechanical testing and measured micro-CT properties to evaluate the degree of osteoporosis. Levels of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRACP), and the ratio of ALP to TRACP both in serum and bone were measured for the evaluation of the bone turnover rate. The bone mRNA and protein expression of ATP6v0d2, IGF-1, BMP2, M-CSF, Wnt5a and TGF-β1 were detected by western blotting (WB), immunofluorescence (IF) and quantitative real time polymerase chain reaction (qRT-PCR) for evaluating bone metabolism in the bone microenvironment. The MLP-ANN model was constructed and used to evaluate the importance of related parameters and the comprehensive action of CaD. Our data showed that bone mass, BMD, maximal load, ultimate displacement, ALP and TRACP in serum and tibia, and the protein and mRNA expressions of ATP6v0d2, IGF-1, BMP2, M-CSF, Wnt5a and TGF-β1 in tibia reached a peak in 6 m rats, and then were gradually decreased with the increase of age to the lowest in 17 m rats. This study demonstrated the degeneration of the bone structure and bone metabolism in SOP rats during the aging process of rats aged 3 to 17 months. CaD could effectively increase bone mass and bone strength, alleviate the degradation of the bone microstructure and rebalance bone remodeling. In addition, the MLP model was a comprehensive method for evaluating the effects of drugs on SOP, which provided a new direction for future drug and nutrition evaluation.
老年性骨质疏松症(SOP)是一种与自然衰老过程中骨骼系统退行性变化相关的疾病。年龄增长是其发病机制的一个重要因素。本实验旨在基于多层感知(MLP)-人工神经网络(ANN)方法评估钙与维生素 D3(CaD)对 SOP 的综合作用。15 月龄雄性 Sprague-Dawley 大鼠给予 CaD 2 个月,3、6、9、12、15 和 17 月龄大鼠分别作为成熟或衰老对照组。我们检测骨量和骨矿物质密度(BMD),进行生物力学测试和测量 micro-CT 特性,以评估骨质疏松程度。检测血清和骨组织中碱性磷酸酶(ALP)和抗酒石酸酸性磷酸酶(TRACP)的水平,以及两者的比值,以评估骨转换率。通过 Western blot(WB)、免疫荧光(IF)和定量实时聚合酶链反应(qRT-PCR)检测骨微环境中骨代谢的骨 mRNA 和蛋白表达,包括 ATP6v0d2、IGF-1、BMP2、M-CSF、Wnt5a 和 TGF-β1。构建 MLP-ANN 模型,用于评估相关参数的重要性和 CaD 的综合作用。我们的数据表明,3 至 17 月龄大鼠的骨量、BMD、最大载荷、最大位移、血清和胫骨中的 ALP 和 TRACP,以及胫骨中的 ATP6v0d2、IGF-1、BMP2、M-CSF、Wnt5a 和 TGF-β1 的蛋白和 mRNA 表达在 6 月龄大鼠中达到峰值,然后随着年龄的增长逐渐下降,在 17 月龄大鼠中降至最低。本研究表明,在 3 至 17 月龄大鼠衰老过程中,SOP 大鼠的骨结构和骨代谢发生退化。CaD 可有效增加骨量和骨强度,减轻骨微结构降解,重新平衡骨重塑。此外,MLP 模型是评估药物对 SOP 影响的综合方法,为未来药物和营养评估提供了新的方向。