Medium to low intensity exercise interferes with the expression of LncRNA HOTAIR in chondrocytes in high-fat-fed mice with knee joint damage

doi:10.12307/2024.221

Abstract

Abstract: BACKGROUND: Low to moderate intensity aerobic exercise can help protect knee cartilage. Long-chain non-coding RNAs are crucial for gene regulation. Among them, HOTAIR can activate numerous transcriptional co-repressors to repress the activation of certain genes.
OBJECTIVE: To detect the expression levels of HOX transcript antisense RNA (HOTAIR) and other related factors in chondrocytes of high fat-fed mice and after low to moderate intensity exercise intervention, and to investigate their role in cartilage injury and sports rehabilitation.
METHODS: Thirty C57BL/6 male mice were randomly divided into control group (normal feeding), high fat feeding group and high fat feeding plus treadmill exercise group, with 10 mice in each group. The mice in the high fat feeding plus treadmill exercise group were subjected to an 8-week low to middle intensity treadmill exercise, and the mice in the other two groups were caged. During this period, body mass was weighed every week on Sunday. After the 8-week exercise, both lower extremities of mice were taken, and the knee joint was scanned using Micro CT to make a 3D femoral condyle image to obtain relevant parameters. Hematoxylin-eosin and safranin O-fast green staining of the knee joint were performed for Mankin and Osteoarthritis Research Society International (OARSI) scoring. RT-PCR was performed to detect the mRNA levels of cartilage metabolic indicators and lipid metabolism indicators, including type II collagen, matrix metalloproteinase 13, interleukin 1, low-density lipoprotein receptor-related protein 5, HOTAIR and its downstream factor lysine specific demethylase 1.
RESULTS AND CONCLUSION: The body mass of high fat-fed mice were higher than that of the control group (P < 0.01), and the body mass of the high fat feeding plus treadmill exercise group was lower than that of the high fat feeding group (P < 0.05). The connectivity density of high fat-fed mice was higher than that of the control group (P < 0.01). Mankin and OARSI scores of the high fat feeding were higher than those of the control group (P < 0.01) and high fat feeding plus treadmill exercise group (P < 0.05). The mRNA level of type II collagen was higher in the control group than the high fat feeding plus treadmill exercise group (P < 0.05) and high fat feeding group (P < 0.01) as well as higher in the high fat feeding plus treadmill exercise group than the high fat feeding group (P < 0.01). The mRNA levels of matrix metalloproteinase 13, interleukin 1, low-density lipoprotein receptor-related protein 5, HOTAIR and lysine specific demethylase 1 were higher in the high fat feed group than the control group and high fat feeding plus treadmill exercise group (P < 0.01). To conclude, high fat feeding can increase the bone substance of the femoral condyle, lead to knee cartilage wear, and cause chondrocyte metabolism disorder. HOTAIR is highly expressed in this process. An 8-week low to middle intensity treadmill exercise can reduce body mass, alleviate knee cartilage wear, improve chondrocyte function and down-regulate HOTAIR expression in mice.

Key words: HOTAIR, high fat, knee osteoarthritis, moderate to low intensity exercise, Micro CT, LncRNAs

CLC Number:

Zhang Huizhen, Wu Wei, Luo Haitao. Medium to low intensity exercise interferes with the expression of LncRNA HOTAIR in chondrocytes in high-fat-fed mice with knee joint damage[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(11): 1684-1689.

Figures/Tables 7

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