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Screening of potential biomarkers and metabolic pathways of knee osteoarthritis in rats / 中华地方病学杂志
Chinese Journal of Endemiology ; (12): 524-529, 2021.
Article in Chinese | WPRIM | ID: wpr-909045
ABSTRACT

Objective:

To screen differential metabolites and metabolic pathways which are related to knee osteoarthritis in rats, and to provide clues for further study of biomarkers of osteoarthritis.

Methods:

Sixty SPF male SD rats were divided into model and control groups according to their body weight (300 - 350 g) by random number table method, with 30 rats in each group. The experimental periods were 4, 8 and 12 weeks, each period included 10 rats in each group. The left knee joints of rats in the model group were operated by the modified Hulth method. After 5 d, rats in the model group were driven to move for 30 min every day. All rats were fed ordinary solid fodder and drank tap water. At the end of the experimental period, the knee joints and blood samples of rats were collected. Hematoxylin-eosin (HE) staining was used to observe histopathological changes of knee joint, ultra-performance liquid chromatography quadrupole time-flight mass spectrometry (UPLC-Q-TOF-MS) was used to detect small molecule metabolites in serum, and multivariate statistical analysis and database comparison were used to screen the differential metabolites and related metabolic pathways associated with osteoarthritis.

Results:

In the model group, the articular cartilage of knee was thinned, the surface was roughness, defect or peeling, chondrocytes were degeneration, necrosis and deletion, and the lesions were aggravated with prolonged experimental period. A total of 11 serum differential metabolites related to osteoarthritis were screened out, including selenocysteine, 6-hydroxymelatonin, γ-glutamylcysteine, arachidonic acid, sphinganine, leukotriene A4, leukotriene B4, 11,12-epoxy-eicostrienoic acid (11,12-EpETrE), lysopc, ceramide and N-arachidonoyl glycine. Among them, 9 metabolites were screened out at 4 weeks, compared with the control group, 5 metabolites were increased and 4 metabolites were decreased in the model group; 8 metabolites were screened out at 8 weeks, compared with the control group, 2 metabolites were increased and 6 metabolites were decreased in the model group; 8 metabolites were screened out at 12 weeks, compared with the control group, 5 metabolites were increased and 3 metabolites were decreased in the model group. The most relevant metabolic pathways related to osteoarthritis were sphingolipid metabolic pathway and arachidonic acid metabolic pathway. Sphinganine and ceramide were belonged to sphingolipid metabolic pathway, whereas arachidonic acid, leukotriene A4 and leukotriene B4 were belonged to arachidonic acid metabolic pathway.

Conclusions:

The progression of osteoarthritis can affect the composition and level of serum metabolite profile. Eleven serum differential metabolites are involved in sphingolipid metabolic pathway and arachidonic acid metabolic pathway, which are related to the occurrence and development of osteoarthritis.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Diagnostic study / Screening study Language: Chinese Journal: Chinese Journal of Endemiology Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Diagnostic study / Screening study Language: Chinese Journal: Chinese Journal of Endemiology Year: 2021 Type: Article