Research progress on the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

CHEN Quan , WU Limin , DAWA Cili ,  SHEN Bin

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China;

Corresponding author：

SHEN Bin, Email: shenbin_1971@163.com

Keywords：

Osteoarthritis; chondrocyte; mitochondrial homeostasis; mitochondrial biogenesis; mitochondrial dynamics; mitochondrial autophagy

DOI：

10.7507/1002-1892.202303006

Video：

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Objective To summarize the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis (OA) and analyze its application prospects. Methods The recent literature at home and abroad was reviewed to summarize the mechanism of mitochondrial homeostasis imbalance, the relationship between mitochondrial homeostasis imbalance and the pathogenesis of OA, and the application prospect in the treatment of OA. Results Recent studies have shown that mitochondrial homeostasis imbalance, which is caused by abnormal mitochondrial biogenesis, the imbalance of mitochondrial redox, the imbalance of mitochondrial dynamics, and damaged mitochondrial autophagy of chondrocytes, plays an important role in the pathogenesis of OA. Abnormal mitochondrial biogenesis can accelerate the catabolic reaction of OA chondrocytes and aggravate cartilage damage. The imbalance of mitochondrial redox can lead to the accumulation of reactive oxygen species (ROS), inhibit the synthesis of extracellular matrix, induce ferroptosis and eventually leads to cartilage degradation. The imbalance of mitochondrial dynamics can lead to mitochondrial DNA mutation, decreased adenosine triphosphate production, ROS accumulation, and accelerated apoptosis of chondrocytes. When mitochondrial autophagy is damaged, dysfunctional mitochondria cannot be cleared in time, leading to ROS accumulation, which leads to chondrocyte apoptosis. It has been found that substances such as puerarin, safflower yellow, and astaxanthin can inhibit the development of OA by regulating mitochondrial homeostasis, which proves the potential to be used in the treatment of OA. Conclusion The mitochondrial homeostasis imbalance in chondrocytes is one of the most important pathogeneses of OA, and further exploration of the mechanisms of mitochondrial homeostasis imbalance is of great significance for the prevention and treatment of OA.

Citation： CHEN Quan, WU Limin, DAWA Cili, SHEN Bin. Research progress on the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis. Chinese Journal of Reparative and Reconstructive Surgery, 2023, 37(6): 748-757. doi: 10.7507/1002-1892.202303006 Copy

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1. Vinatier C, Merceron C, Guicheux J. Osteoarthritis: from pathogenic mechanisms and recent clinical developments to novel prospective therapeutic options. Drug Discov Today, 2016, 21(12): 1932-1937.
2. Ruiz D, Koenig L, Dall TM, et al. The direct and indirect costs to society of treatment for end-stage knee osteoarthritis. J Bone Joint Surg (Am), 2013, 95(16): 1473-1480.
3. Friedman JR, Nunnari J. Mitochondrial form and function. Nature, 2014, 505(7483): 335-343.
4. Blanco FJ, Rego I, Ruiz-Romero C. The role of mitochondria in osteoarthritis. Nat Rev Rheumatol, 2011, 7(3): 161-169.
5. Blanco FJ, Valdes AM, Rego-Pérez I. Mitochondrial DNA variation and the pathogenesis of osteoarthritis phenotypes. Nat Rev Rheumatol, 2018, 14(6): 327-340.
6. López-Armada MJ, Caramés B, Martín MA, et al. Mitochondrial activity is modulated by TNFalpha and IL-1beta in normal human chondrocyte cells. Osteoarthritis Cartilage, 2006, 14(10): 1011-1022.
7. Vázquez-Mosquera ME, Fernández-Moreno M, Cortés-Pereira E, et al. Oleate prevents palmitate-induced mitochondrial dysfunction in chondrocytes. Front Physiol, 2021, 12: 670753. doi: 10.3389/fphys.2021.670753.
8. Wang Y, Zhao X, Lotz M, et al. Mitochondrial biogenesis is impaired in osteoarthritis chondrocytes but reversible via peroxisome proliferator-activated receptor γ coactivator 1α. Arthritis Rheumatol, 2015, 67(8): 2141-2153.
9. Jamwal S, Blackburn JK, Elsworth JD. PPARγ/PGC1α signaling as a potential therapeutic target for mitochondrial biogenesis in neurodegenerative disorders. Pharmacol Ther, 2021, 219: 107705. doi: 10.1016/j.pharmthera.2020.107705.
10. Jornayvaz FR, Shulman GI. Regulation of mitochondrial biogenesis. Essays Biochem, 2010, 47: 69-84.
11. Li PA, Hou X, Hao S. Mitochondrial biogenesis in neurodegeneration. J Neurosci Res, 2017, 95(10): 2025-2029.
12. 周圣梁, 斯海波, 彭琳博, 等. 软骨细胞线粒体生物发生在骨关节炎发病机制中的作用. 中国修复重建外科杂志, 2022, 36(2): 242-248.
13. Chang HC, Guarente L. SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab, 2014, 25(3): 138-145.
14. Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol, 2018, 19(2): 121-135.
15. Salminen A, Kaarniranta K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev, 2012, 11(2): 230-241.
16. Rebelo AP, Dillon LM, Moraes CT. Mitochondrial DNA transcription regulation and nucleoid organization. J Inherit Metab Dis, 2011, 34(4): 941-951.
17. Picca A, Mankowski RT, Burman JL, et al. Mitochondrial quality control mechanisms as molecular targets in cardiac ageing. Nat Rev Cardiol, 2018, 15(9): 543-554.
18. Picca A, Lezza AM. Regulation of mitochondrial biogenesis through TFAM-mitochondrial DNA interactions: Useful insights from aging and calorie restriction studies. Mitochondrion, 2015, 25: 67-75.
19. Kang C, Li Ji L. Role of PGC-1α signaling in skeletal muscle health and disease. Ann N Y Acad Sci, 2012, 1271(1): 110-117.
20. Zhao X, Petursson F, Viollet B, et al. Peroxisome proliferator-activated receptor γ coactivator 1α and FoxO3A mediate chondroprotection by AMP-activated protein kinase. Arthritis Rheumatol, 2014, 66(11): 3073-3082.
21. Soto-Hermida A, Fernández-Moreno M, Pértega-Díaz S, et al. Mitochondrial DNA haplogroups modulate the radiographic progression of Spanish patients with osteoarthritis. Rheumatol Int, 2015, 35(2): 337-344.
22. Petursson F, Husa M, June R, et al. Linked decreases in liver kinase B1 and AMP-activated protein kinase activity modulate matrix catabolic responses to biomechanical injury in chondrocytes. Arthritis Res Ther, 2013, 15(4): R77. doi: 10.1186/ar4254.
23. Chen LY, Wang Y, Terkeltaub R, et al. Activation of AMPK-SIRT3 signaling is chondroprotective by preserving mitochondrial DNA integrity and function. Osteoarthritis Cartilage, 2018, 26(11): 1539-1550.
24. Hardie DG. AMP-activated protein kinase: maintaining energy homeostasis at the cellular and whole-body levels. Annu Rev Nutr, 2014, 34: 31-55.
25. Matsuzaki T, Matsushita T, Takayama K, et al. Disruption of Sirt1 in chondrocytes causes accelerated progression of osteoarthritis under mechanical stress and during ageing in mice. Ann Rheum Dis, 2014, 73(7): 1397-1404.
26. Wang J, Wang K, Huang C, et al. SIRT3 Activation by dihydromyricetin suppresses chondrocytes degeneration via maintaining mitochondrial homeostasis. Int J Biol Sci, 2018, 14(13): 1873-1882.
27. Torrens-Mas M, Pons DG, Sastre-Serra J, et al. SIRT3 silencing sensitizes breast cancer cells to cytotoxic treatments through an increment in ROS production. J Cell Biochem, 2017, 118(2): 397-406.
28. Wang L, Shan H, Wang B, et al. Puerarin attenuates osteoarthritis via upregulating AMP-activated protein kinase/proliferator-activated receptor-γ coactivator-1 signaling pathway in osteoarthritis rats. Pharmacology, 2018, 102(3-4): 117-125.
29. Masuda I, Koike M, Nakashima S, et al. Apple procyanidins promote mitochondrial biogenesis and proteoglycan biosynthesis in chondrocytes. Sci Rep, 2018, 8(1): 7229. doi: 10.1038/s41598-018-25348-1.
30. Wang C, Gao Y, Zhang Z, et al. Safflower yellow alleviates osteoarthritis and prevents inflammation by inhibiting PGE2 release and regulating NF-κB/SIRT1/AMPK signaling pathways. Phytomedicine, 2020, 78: 153305. doi: 10.1016/j.phymed.2020.153305.
31. Li J, Zhang B, Liu WX, et al. Metformin limits osteoarthritis development and progression through activation of AMPK signalling. Ann Rheum Dis, 2020, 79(5): 635-645.
32. Adam-Vizi V, Chinopoulos C. Bioenergetics and the formation of mitochondrial reactive oxygen species. Trends Pharmacol Sci, 2006, 27(12): 639-645.
33. Hirst J. Mitochondrial complex I. Annu Rev Biochem, 2013, 82: 551-575.
34. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol, 2003, 552(Pt 2): 335-344.
35. Gao M, Yi J, Zhu J, et al. Role of Mitochondria in Ferroptosis. Mol Cell, 2019, 73(2): 354-363.
36. Lei G, Mao C, Yan Y, et al. Ferroptosis, radiotherapy, and combination therapeutic strategies. Protein Cell, 2021, 12(11): 836-857.
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Chinese Journal of Reparative and Reconstructive Surgery

Research progress on the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis

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