Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, 03759, Republic of Korea.
Department of Chemistry, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Sci Rep. 2018 May 25;8(1):8127. doi: 10.1038/s41598-018-26322-7.
Age-related osteoporosis is characterized by reduced bone mineralization and reduced bone strength, which increases the risk of fractures. We examined metabolic changes associated with age-related bone loss by profiling lipids and polar metabolites in tibia and femur bone tissues from young (5 months old) and old (28 months old) male C57BL/6J mice using ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry. Partial least-squares discriminant analysis showed clear differences in metabolite levels in bone tissues of young and old mice. We identified 93 lipid species, including free fatty acids, sphingolipids, phospholipids, and glycerolipids, that were significantly altered in bone tissues of old mice. In addition, the expression of 26 polar metabolites differed significantly in bone tissues of old mice and young mice. Specifically, uremic toxin metabolite levels (p-cresyl sulfate, hippuric acid, and indoxylsulfate) were higher in bone tissues of old mice than in young mice. The increase in p-cresyl sulfate, hippuric acid, and indoxylsulfate levels were determined using targeted analysis of plasma polar extracts to determine whether these metabolites could serve as potential osteoporosis biomarkers. This study demonstrates that LC-MS-based global profiling of lipid and polar metabolites can elucidate metabolic changes that occur during age-related bone loss and identify potential biomarkers of osteoporosis.
年龄相关性骨质疏松症的特征是骨矿化减少和骨强度降低，从而增加骨折的风险。我们使用超高效液相色谱-四极杆飞行时间质谱联用技术，对来自年轻（5 个月大）和年老（28 个月大）雄性 C57BL/6J 小鼠的胫骨和股骨骨组织中的脂质和极性代谢物进行分析，以研究与年龄相关的骨丢失相关的代谢变化。偏最小二乘判别分析显示，年轻和年老小鼠骨组织中的代谢物水平存在明显差异。我们鉴定出 93 种脂质种类，包括游离脂肪酸、鞘脂类、磷脂和甘油酯，这些脂质在年老小鼠的骨组织中明显改变。此外，26 种极性代谢物在年老小鼠和年轻小鼠的骨组织中的表达也有明显差异。具体而言，年老小鼠骨组织中的尿毒症毒素代谢物水平（对羟苯磺酸、马尿酸和吲哚硫酸）高于年轻小鼠。通过对血浆极性提取物进行靶向分析来确定 p- 对羟苯磺酸、马尿酸和吲哚硫酸水平的增加，以确定这些代谢物是否可以作为潜在的骨质疏松症生物标志物。本研究表明，基于 LC-MS 的脂质和极性代谢物的全局分析可以阐明与年龄相关的骨丢失过程中发生的代谢变化，并确定骨质疏松症的潜在生物标志物。
