Department of Orthopedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Cartilage Regeneration Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Aging (Albany NY). 2022 Jul 1;14(13):5366-5375. doi: 10.18632/aging.204066.
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.
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), , 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.
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, , the reduced autophagy and elevated cell senescence in human chondrocyte.
Interfering with TRB3 expression in cartilage may serve as a target in the prevention and treatment of age-related osteoarthritis.
骨关节炎与衰老密切相关。研究发现 Tribbles 同源物 3（TRB3）具有年龄相关性表达，并参与细胞增殖、分化和纤维化的调控。本研究旨在探讨 TRB3 与骨关节炎中软骨自噬和衰老的潜在关系。
收集接受关节置换术的骨关节炎患者和尸体供体的软骨组织样本。通过免疫组织化学和 Western blot（WB）分析骨关节炎软骨组织中的自噬和衰老相关蛋白，以验证 TRB3 在自噬、细胞衰老和炎症过程中的作用。使用小干扰 RNA（siRNA）对细胞中的 TRB3 进行敲低。
我们发现骨关节炎患者组织样本中的 p62 水平升高，微管相关蛋白 1A/1B-轻链 3（LC3）和 beclin-1 水平降低，p16 和 p21 水平升高，表明自噬减少和细胞衰老增加。TRB3 敲低显著挽救了人软骨细胞中降低的自噬和升高的细胞衰老。
干扰软骨中的 TRB3 表达可能成为预防和治疗与年龄相关的骨关节炎的靶点。
