Author links open overlay panel,
,
,
,
,
,
,
,
,
,
,
,
,
- a
- Key Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory of Brain Science Research and Transformation in Tropical Environment of Hainan Province, Hainan Provincial Stem Cell Research Institute, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, 571199, China
- b
- Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China
- c
- Plastic Surgery, Second Affiliated Hospital of Hainan Medical University, Haikou, 570100, China
- d
- Zhongke Comprehensive Medical Transformation Center Research Institute (Hainan) Co., Ltd, Haikou, 571199, China
- e
- Department of Pharmacology, Zibo Hospital of Traditional Chinese Medicine, Zibo, 255300, China
- f
- School of Clinical Medicine, Jining Medical University, Jining, 272002, China
- g
- Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Hainan Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, 571199, China
- h
- Key Laboratory of Emergency and Trauma of Ministry of Education, Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital, Hainan Medical University, Haikou, 571199, China
- i
- The Second Clinical College, Hainan Medical University, Haikou, 571199, China
Received 28 May 2024, Revised 17 September 2024, Accepted 26 September 2024, Available online 11 October 2024, Version of Record 11 October 2024.
https://doi.org/10.1016/j.jot.2024.09.011
Abstract
Osteoarthritis (OA) is a degenerative disease that affects multiple cells and associated extracellular matrix (ECM). Chondrocytes and chondroextracellular matrix together constitute articular cartilage tissue. Any factors that affect the activity of chondrocytes and destroy the metabolic balance of the chondrocyte ECM will lead to the inability of articular cartilage to perform normal functions. The articular subchondral bone and articular cartilage must be coordinated to resist enough friction and mechanical stress, so the articular subchondral bone lesion will aggravate the articular cartilage defect and vice versa. Synoviocytes, including fibroblast-like synoviocytes (FLSs) and synovial macrophages at the joint, are also important factors that cause low-grade chronic progressive inflammation of OA. Regulation of phenotype transformation of synovial macrophages has become another possible target for the clinical treatment of OA. Ubiquitination and deubiquitination are the main post-translational protein modification pathways in the human body, which are widely involved in multiple signaling pathways and physiological processes. Naturally, they also play a very important regulatory role in the occurrence and development of OA. These effects are summarized in this review, including (A) regulating the aging and apoptosis of chondrocytes, FLSs and osteoblasts; (B) regulation of ECM degradation; (C) regulation of macrophage phenotypic transformation; (D) modulation of skeletal muscle and adipose tissues. Ubiquitination targeting drugs for OA treatment are also listed. Depending on the high efficiency of ubiquitination and deubiquitination, understanding OA-related ubiquitination pathways can help design more efficient drugs to treat OA and provide more potential targets for clinical treatment.
Graphical abstract
Ubiquitination and deubiquitination participate in the homeostasis between healthy joints and osteoarthritic joints through regulating senescence, apoptosis and autophagy of chondrocytes, fibroblast-like synoviocytes, osteoblasts, macrophages, skeletal muscle and adipose tissue. Digoxin, 6-Gingerol, Resveratrol, Spermidine, Alpinetin and Melatonin are potential therapeutic drugs.
