Screening of potential biomarkers and metabolic pathways in urine of rats with osteoarthritis
10.3760/cma.j.cn231583-20240420-00102
- VernacularTitle:骨关节炎大鼠尿液潜在生物标志物及代谢通路筛选
- Author:
Yumeng WANG
1
;
Lihua WANG
Author Information
1. 浙江省宁波市北仑区人民医院病案统计室，宁波315800
- Publication Type:Journal Article
- Keywords:
Osteoarthritis;
Urine;
Biomarkers;
Metabolic pathway;
Rats
- From:
Chinese Journal of Endemiology
2025;44(3):192-197
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To screen differential metabolites and their metabolic pathways related to osteoarthritis, and to provide clues for further study of biomarkers of osteoarthritis.Methods:Using group design, 60 male SD rats (weighting 300 - 350 g) were divided into a model group and a control group according to random number table method, with 30 rats in each group. The experimental periods were 4, 8 and 12 weeks, respectively, with 10 rats per group per period. The left knee joint of rats of the model group rats underwent modified Hulth method surgery. After 5 days, the rats were driven to move for 30 minutes a day. At the end of the experiment, 24 h urine of rats in two groups was collected. Small molecule metabolites in urine were detected by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometer, and the differential metabolites and metabolic pathways related to osteoarthritis were screened by multivariate statistical analysis and database comparison.Results:A total of 9 differential metabolites associated with osteoarthritis were screened out in urine. Among them, 9 metabolites were screened out at 4 weeks of the experiment. Compared with the control group, the model group had higher levels of kynurenine, citric acid, cysteic acid, malonyl carnitine, ubiquinone-2, L-cystathionine and L-aspartic acid [26 317 (19 439, 33 297) vs 3 595 (512, 23 556), 7 137 (2 901, 9 252) vs 1 854 (660, 4 754), 6 625 ± 4 468 vs 3 006 ± 2 636, 4 254 (2 949, 7 850) vs 2 223 (1 230, 3 390), 14 558 (6 605, 26 047) vs 5 908 (1 172, 10 560), 4 492 (2 541, 33 796) vs 1 038 (885, 2 938), 3 038 ± 2 282 vs 1 286 ± 1 264], while the levels of 5-L-glutamyltaurine and S-adenosylmethionine were lower (2 145 ± 658 vs 6 457 ± 5 457, 872 ± 582 vs 5 572 ± 5 362, P < 0.05). At 8 weeks of the experiment, 7 metabolites were screened out. Compared with the control group, the model group had higher levels of kynurenine, citric acid, cysteic acid, 5-L-glutamyltaurine, malonyl carnitine and ubiquinone-2, while the level of L-cystathionine was lower ( P < 0.05). At 12 weeks of the experiment, 4 metabolites were screened out. Compared with the control group, the model group had higher level of 5-L-glutamyltaurine, while the levels of kynurenine, citric acid, and cysteic acid were lower ( P < 0.05). Two metabolic pathways related to osteoarthritis were identified, namely the cysteine and methionine metabolic pathway, and the arginine and proline metabolic pathway. Among them, cysteic acid, S-adenosylmethionine and L-cystathionine belonged to the cysteine and methionine metabolic pathway, while L-aspartic acid and S-adenosylmethionine belonged to the arginine and proline metabolic pathway. Conclusions:Kynurenine, citric acid, cysteic acid and 5-L-glutamyltaurine are differential metabolites associated with osteoarthritis and may serve as urinary metabolic biomarkers for osteoarthritis. The metabolic pathways of cysteine and methionine, arginine and proline may be closely related to the occurrence and development of osteoarthritis.
