Journal
PHARMACOLOGICAL RESEARCH
Volume 166, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2021.105497
Keywords
Osteoarthritis; Chondrocytes; Mitochondrial quality control; AMPK; SIRT3; Positive feedback loop
Categories
Funding
- Health and Family Planning Commission of Sichuan Province [20PJ056]
- National Natural Science Foundation of China [81802210, 81974347]
- Department of Science and Technology of Sichuan Province [2021YFS0122]
- National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University [Z2018B20]
Ask authors/readers for more resources
Regulation of chondrocyte mitochondrial quality control may play a crucial role in the pathogenesis and progression of osteoarthritis.
Osteoarthritis (OA) is a major cause of disability in the elderly population and represents a significant public health problem and socioeconomic burden worldwide. However, no disease-modifying therapeutics are currently available for OA due to an insufficient understanding of the pathogenesis of this disability. As a unique cell type in cartilage, chondrocytes are essential for cartilage homeostasis and play a critical role in OA pathogenesis. Mitochondria are important metabolic centers in chondrocytes and contribute to cell survival, and mitochondrial quality control (MQC) is an emerging mechanism for maintaining cell homeostasis. An increasing number of recent studies have demonstrated that dysregulation of the key processes of chondrocyte MQC, which involve mitochondrial redox, biogenesis, dynamics, and mitophagy, is associated with OA pathogenesis and can be regulated by the chondroprotective molecules 5' adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 3 (SIRT3). Moreover, AMPK and SIRT3 regulate each other, and their expression and activity are always consistent in chondrocytes, which suggests the existence of an AMPK-SIRT3 positive feedback loop (PFL). Although the precise mechanisms are not fully elucidated and need further validation, the current literature indicates that this AMPK-SIRT3 PFL regulates OA development and progression, at least partially by mediating chondrocyte MQC. Therefore, understanding the mechanisms of AMPK-SIRT3 PFL-mediated chondrocyte MQC in OA pathogenesis might yield new ideas and potential targets for subsequent research on the OA pathomechanism and therapeutics.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available