Saberi, M., Zhang, X. & Mobasheri, A. Targeting mitochondrial dysfunction with small molecules in intervertebral disc aging and degeneration. GeroScience 43, 517–537 (2021). https://doi.org/10.1007/s11357-021-00341-1
Targeting mitochondrial dysfunction with small molecules in intervertebral disc aging and degeneration
|Author:||Saberi, Morteza1; Zhang, Xiaolei2,3; Mobasheri, Ali4,5,6,7|
1Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
2Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
3Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China
4Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
5Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
6Departments of Orthopedics, Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
7Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
|Online Access:||PDF Full Text (PDF, 2 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2021061136653
|Publish Date:|| 2021-06-11
The prevalence of rheumatic and musculoskeletal diseases (RMDs) including osteoarthritis (OA) and low back pain (LBP) in aging societies present significant cost burdens to health and social care systems. Intervertebral disc (IVD) degeneration, which is characterized by disc dehydration, anatomical alterations, and extensive changes in extracellular matrix (ECM) composition, is an important contributor to LBP. IVD cell homeostasis can be disrupted by mitochondrial dysfunction. Mitochondria are the main source of energy supply in IVD cells and a major contributor to the production of reactive oxygen species (ROS). Therefore, mitochondria represent a double-edged sword in IVD cells. Mitochondrial dysfunction results in oxidative stress, cell death, and premature cell senescence, which are all implicated in IVD degeneration. Considering the importance of optimal mitochondrial function for the preservation of IVD cell homeostasis, extensive studies have been done in recent years to evaluate the efficacy of small molecules targeting mitochondrial dysfunction. In this article, we review the pathogenesis of mitochondrial dysfunction, aiming to highlight the role of small molecules and a selected number of biological growth factors that regulate mitochondrial function and maintain IVD cell homeostasis. Furthermore, molecules that target mitochondria and their mechanisms of action and potential for IVD regeneration are identified. Finally, we discuss mitophagy as a key mediator of many cellular events and the small molecules regulating its function.
|Pages:||517 - 537|
|Type of Publication:||
A2 Review article in a scientific journal
|Field of Science:||
3121 General medicine, internal medicine and other clinical medicine
Open access funding provided by University of Oulu including Oulu University Hospital. A.M. has received funding from the following sources: The European Commission Framework 7 programme (EU FP7; HEALTH.2012.2.4.5-2, project number 305815; Novel Diagnostics and Biomarkers for Early Identification of Chronic Inflammatory Joint Diseases). The Innovative Medicines Initiative Joint Undertaking under grant agreement No. 115770, resources of which are composed of financial contribution from the European Union’s Seventh Framework programme (FP7/2007-2013) and EFPIA companies’ in-kind contribution. A.M. also wishes to acknowledge funding from the European Commission through a Marie Curie Intra-European Fellowship for Career Development grant (project number 625746; acronym: CHONDRION; FP7-PEOPLE-2013-IEF). A.M. also wishes to acknowledge financial support from the European Structural and Social Funds (ES Struktūrinės Paramos) through the Research Council of Lithuania (Lietuvos Mokslo Taryba) according to the activity “Improvement of researchers” qualification by implementing world-class R&D projects of Measure No. 09.3.3-LMT-K-712 (grant application code: 09.3.3-LMT-K-712-01-0157, agreement No. DOTSUT-215) and the new funding programme: Attracting Foreign Researchers for Research Implementation (2018-2022). X.Z. wishes to acknowledge funding from the Zhejiang Provincial Natural Science Foundation of China (LGF21H060011) and Lin He’s New Medicine and Clinical Translation Academician Workstation Research Fund.
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