Oxidized LDL accelerates cartilage destruction and inflammatory chondrocyte death in osteoarthritis by disrupting the TFEB-regulated autophagy-lysosome pathway
Journal article
Lee, J., Kim, Y., Jhun, J., Na, H., Um, In Gyu, Choi, J., Woo, J., Kim, S., Shetty, A., Kim, S. and Cho, M. 2024. Oxidized LDL accelerates cartilage destruction and inflammatory chondrocyte death in osteoarthritis by disrupting the TFEB-regulated autophagy-lysosome pathway. Immune Network. 24 (3). https://doi.org/10.4110/in.2024.24.e15
Authors | Lee, J., Kim, Y., Jhun, J., Na, H., Um, In Gyu, Choi, J., Woo, J., Kim, S., Shetty, A., Kim, S. and Cho, M. |
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Abstract | Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes. |
Keywords | Osteoarthritis; Dyslipidemia; Low-density lipoprotein; Autophagy; Necroptis |
Year | 2024 |
Journal | Immune Network |
Journal citation | 24 (3) |
Publisher | The Korean Association of Immunologists |
ISSN | 1598-2629 |
2092-6685 | |
Digital Object Identifier (DOI) | https://doi.org/10.4110/in.2024.24.e15 |
Official URL | https://immunenetwork.org/DOIx.php?id=10.4110/in.2024.24.e15 |
Funder | National Research Foundation of Korea |
Korea Health Industry Development Institute | |
Publication dates | |
Online | 12 Apr 2024 |
Publication process dates | |
Accepted | 03 Apr 2024 |
Deposited | 08 Jul 2024 |
Output status | Published |
https://repository.canterbury.ac.uk/item/98545/oxidized-ldl-accelerates-cartilage-destruction-and-inflammatory-chondrocyte-death-in-osteoarthritis-by-disrupting-the-tfeb-regulated-autophagy-lysosome-pathway
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