Research Paper Volume 14, Issue 13 pp 5366—5375
High TRB3 expression induces chondrocyte autophagy and senescence in osteoarthritis cartilage
- 1 Department of Orthopedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
- 2 Cartilage Regeneration Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
- 3 Digital Medicine Institute, Nanjing Medical University, Nanjing, Jiangsu, China
Received: October 1, 2021 Accepted: June 24, 2022 Published: July 1, 2022
https://doi.org/10.18632/aging.204066How to Cite
Copyright: © 2022 Gu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: Osteoarthritis is closely related to aging. Tribbles homologue 3 (TRB3) is found to display age-related expression and contributes to the regulation of cell proliferation, differentiation and fibrosis. In this study, we aimed to investigate the potential involvement of TRB3 in cartilage autophagy and aging in osteoarthritis.
Methods: Cartilage tissue samples were collected from osteoarthritis patients who received joint replacement and cadaveric donors. In osteoarthritis cartilage tissue, we analyzed autophagy- and senescence-associated proteins using immunohistochemistry and western blot (WB), in vitro, to confirm the role played by TRB3 in the process of autophagy, cell senescence, and inflammation, small interfering RNA (siRNA) was used for TRB3 knockdown in cells.
Results: We found increased level of p62, decreased level of microtubule-associated protein 1A/1B-light chain 3 (LC3) and beclin-1 in cartilage, and increased level of p16 and p21 in tissue samples collected from osteoarthritis patients, indicating decreased autophagy and increased cell senescence. TRB3 knockdown significantly rescued, in vitro, the reduced autophagy and elevated cell senescence in human chondrocyte.
Conclusions: Interfering with TRB3 expression in cartilage may serve as a target in the prevention and treatment of age-related osteoarthritis.