The Role of Mitochondrial Metabolism, AMPK-SIRT Mediated Pathway, LncRNA and MicroRNA in Osteoarthritis

Hao-Yu Liu; Chi-Fen Chang; Cheng-Chang Lu; Shun-Cheng Wu; Bin Huang; Tsung-Lin Cheng; Sung-Yen Lin; Cheng-Jung Ho; Mon-Juan Lee; Chung-Da Yang; Ying-Chun Wang; Jhong-You Li; Ping-Cheng Liu; Chun-Wang Wei; Lin Kang; Chung-Hwan Chen

doi:10.3390/biomedicines10071477

The Role of Mitochondrial Metabolism, AMPK-SIRT Mediated Pathway, LncRNA and MicroRNA in Osteoarthritis

Biomedicines. 2022 Jun 22;10(7):1477. doi: 10.3390/biomedicines10071477.

Authors

Hao-Yu Liu^{1

2

3

4}, Chi-Fen Chang⁵, Cheng-Chang Lu^{1

2

3

4

6}, Shun-Cheng Wu^{1

3}, Bin Huang⁷, Tsung-Lin Cheng^{1

3

8}, Sung-Yen Lin^{1

2

3

4}, Cheng-Jung Ho^{1

2

3

4

9}, Mon-Juan Lee^{10

11}, Chung-Da Yang¹², Ying-Chun Wang^{2

5

13

14}, Jhong-You Li^{1

2

3

4

6

9}, Ping-Cheng Liu^{1

2

3

4

6}, Chun-Wang Wei¹⁵, Lin Kang¹⁶, Chung-Hwan Chen^{1

2

3

4

12

13

15

17

18}

Affiliations

¹ Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
² Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
³ Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁴ Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁵ Department of Anatomy, School of Medicine, China Medical University, Taichung 40402, Taiwan.
⁶ Department of Orthopedics, Kaohsiung Municipal Siaogang Hospital, Kaohsiung 812, Taiwan.
⁷ Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁸ Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80701, Taiwan.
⁹ Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
¹⁰ Department of Bioscience Technology, Chang Jung Christian University, Tainan 71101, Taiwan.
¹¹ Innovative Research Center of Medicine, Chang Jung Christian University, Tainan 71101, Taiwan.
¹² Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 912301, Taiwan.
¹³ Ph.D. Program in Biomedical Engineering, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
¹⁴ Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan.
¹⁵ Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
¹⁶ Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
¹⁷ Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 80420, Taiwan.
¹⁸ Graduate Institute of Materials Engineering, College of Engineering, National Pingtung University of Science and Technology, Pingtung 912301, Taiwan.

Abstract

Osteoarthritis (OA) is the most common joint disease characterized by degeneration of articular cartilage and causes severe joint pain, physical disability, and impaired quality of life. Recently, it was found that mitochondria not only act as a powerhouse of cells that provide energy for cellular metabolism, but are also involved in crucial pathways responsible for maintaining chondrocyte physiology. Therefore, a growing amount of evidence emphasizes that impairment of mitochondrial function is associated with OA pathogenesis; however, the exact mechanism is not well known. Moreover, the AMP-activated protein kinase (AMPK)-Sirtuin (SIRT) signaling pathway, long non-coding RNA (lncRNA), and microRNA (miRNA) are important for regulating the physiological and pathological processes of chondrocytes, indicating that these may be targets for OA treatment. In this review, we first focus on the importance of mitochondria metabolic dysregulation related to OA. Then, we show recent evidence on the AMPK-SIRT mediated pathway associated with OA pathogenesis and potential treatment options. Finally, we discuss current research into the effects of lncRNA and miRNA on OA progression or inhibition.

Keywords: AMP-activated protein kinase (AMPK); long non-coding RNA (lncRNA); microRNA (miRNA); mitochondria; osteoarthritis; sirtuins (SIRT).

Publication types

Review

Grants and funding

This study was supported in part by the National Health Research Institute (NHRI-EX101-9935EI) of Taiwan, Kaohsiung Medical University (NPUST-KMU-109-P002, NCTUKMU108-BIO-04, KMU-TC108A02-1, KMU-DK105009, KMU-DK(B) 110002 and KMU-111-P005), National Cheng Kung University (NCKUH-11102060), Kaohsiung Municipal Ta-Tung Hospital (KMTTH-109-R014, KMTTH-DK(B) 110002-1 and KMTTH-110-R008), and the Minister of Science and Technology of Taiwan (MOST 110-2314-B-006-037-MY3, 108-2314-B-037-059-MY3 and 110-2314-B-037-029-MY3). The funders had no role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript.