Longbie capsules reduce bone loss in the subchondral bone of rats with comorbid osteoporosis and osteoarthritis by regulating metabolite alterations.
Longbie capsules reduce bone loss in the subchondral bone of rats with comorbid osteoporosis and osteoarthritis by regulating metabolite alterations.
复制标题
DOI：
10.3389/fmed.2023.1256238
复制
发表时间：
2023
影响因子：
3.9
通讯作者：
Liu, Jun
中科院分区：
文献类型：
--
作者：
Liang, Guihong;Zhao, Jinlong;Zhao, Di;Dou, Yaoxing;Huang, Hetao;Yang, Weiyi;Zhou, Guanghui;Gu, Zhuoxu;Pan, Jianke;Liu, Jun
关键词：
随着全球人口老龄化的发展，共病（≥2种疾病）是老年人常见的健康问题。骨关节炎（OA）和骨质疏松症（OP）在老年人中较为常见。针对OA和OP共病缺乏药物治疗。本研究旨在利用代谢组学技术探讨含有多种植物草药的龙鳖胶囊（LBJN）对大鼠OA和OP共病（OA + OP）的疗效及机制。
我们通过双侧卵巢切除联合半月板不稳定手术建立了OA + OP大鼠模型。将30只SD大鼠随机分为5组（每组6只），即假手术组、OA组、OA + OP组、LBJN低剂量组（0.625 g/kg，OA + OP + LB - L组）和LBJN高剂量组（1.25 g/kg，OA + OP + LB - H组）。干预8周后，我们利用微计算机断层扫描（micro - CT）检测骨微结构状态，酶联免疫吸附测定（ELISA）测量骨代谢指标，并采用超高效液相色谱 - 质谱（UPLC - MS）技术进行代谢组学分析。最后，对筛选出的差异表达代谢物进行京都基因与基因组百科全书（KEGG）通路及功能富集分析。
微计算机断层扫描结果显示，LBJN显著改善了OA + OP大鼠软骨下骨的骨密度（BMD）和骨质量，并且LBJN调节血清中骨碱性磷酸酶（BALP）、骨保护素（OPG）和抗酒石酸酸性磷酸酶（TRACP）的表达以维持骨代谢平衡。代谢组学分析表明，OA + OP + LB - H组干预后OA + OP大鼠的代谢轨迹发生显著变化，可鉴定出107种潜在生物标志物。其中，50种代谢物上调（如玉米赤霉醇），57种代谢物下调（如香草酸）。KEGG功能富集结果表明，差异表达代谢物主要涉及氨基酸代谢、脂质代谢和碳水化合物代谢。KEGG通路富集结果表明，LBJN可能通过调节环磷酸腺苷（cAMP）信号通路和叉头框O（FoxO）信号通路对OA + OP大鼠发挥治疗作用。
LBJN可通过调节血清脂质代谢、氨基酸代谢、碳水化合物代谢和雌激素来维持骨代谢平衡，从而减少软骨下骨的骨质流失，这可能是LBJN治疗OA + OP的潜在机制。
With the development of global population aging, comorbidity (≥2 diseases) is a common health problem among elderly people. Osteoarthritis (OA) and osteoporosis (OP) are common in elderly individuals. There is a lack of drug therapy for OA and OP comorbidities. The purpose of this study was to explore the efficacy and mechanism of Longbie capsule (LBJN), which contains various plant herbs, in treating OA and OP comorbidities (OA + OP) in rats using metabolomics techniques. We created an OA + OP rat model through bilateral oophorectomy combined with meniscus instability surgery. Thirty SD rats were randomly divided into five groups (six in each group), namely, the sham group, OA group, OA + OP group, LBJN low-dose group (0.625 g/kg, OA + OP+LB-L group) and LBJN high-dose group (1.25 g/kg, OA + OP+LB-H group). After 8 weeks of intervention, we used micro-CT to detect bone microstructure status, ELISA to measure bone metabolism indicators, and UPLC–MS technology for metabolomics analysis. Finally, the screened differentially expressed metabolites were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and functional enrichment analysis. The micro-CT results showed that LBJN significantly improved the bone mineral density (BMD) and bone quality of subchondral bone in OA + OP rats, and LBJN regulated the expression of bone alkaline phosphatase (BALP), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRACP) in serum to maintain bone metabolism balance. Metabolomics analysis showed that the metabolic trajectory of OA + OP rats after intervention in the OA + OP+LB-H group showed significant changes, and 107 potential biomarkers could be identified. Among them, 50 metabolites were upregulated (such as zeranol) and 57 were downregulated (such as vanillactic acid). The KEGG functional enrichment results indicated that the differentially expressed metabolites are mainly involved in amino acid metabolism, lipid metabolism, and carbohydrate metabolism. The KEGG pathway enrichment results indicated that LBJN may exert therapeutic effects on OA + OP rats by regulating the cAMP signaling pathway, and the FoxO signaling pathway. LBJN can maintain bone metabolism balance by regulating serum lipid metabolism, amino acid metabolism, carbohydrate metabolism, and estrogen, thereby reducing bone loss in subchondral bone, which may be a potential mechanism through which LBJN treats OA + OP.
登录
查看更多内容
骨研究中的代谢组学。
影响因子：
4.1
作者：
Fan J;Jahed V;Klavins K
通讯作者：
Klavins K
影响因子：
2.3
作者：
Chen, Bin;Li, Hong-zhuo
通讯作者：
Li, Hong-zhuo
补肾活血中药治疗膝骨关节炎比非甾体抗炎药更好吗？
DOI：
10.1155/2019/9094515
发表时间：
2019-11-25
影响因子：
--
作者：
Huang, Hetao;Pan, Jianke;Liu, Jun
通讯作者：
Liu, Jun
DOI：
10.1016/j.berh.2022.101810
发表时间：
2022-12-01
期刊：
Best practice & research. Clinical rheumatology
影响因子：
--
作者：
Kennedy, Sarah;Tambiah, Jeyanesh R S;Lane, Nancy E
通讯作者：
Lane, Nancy E
影响因子：
15.9
作者：
Kode, Aruna;Mosialou, Ioanna;Kousteni, Stavroula
通讯作者：
Kousteni, Stavroula