High expression of Piezo1 induces senescence in chondrocytes through calcium ions accumulation

Background: Chondrocytes senescence is closely related to orthopedic degenerative diseases such as osteoarthritis (OA). Calcium ions (Ca2+) accumulation is a common phenomenon in senescent cells, which causes mitochondrial dysfunction and ROS generation to promote the process of senescence. Piezo1 is a mechanosensitive ion channel with a unique affinity for Ca2+. However, the role of Piezo1mediated Ca2+ accumulation in senescent chondrocytes remains unclear. Methods: First, the senescent chondrocytes model was constructed by subcultring primary chondrocytes (P0) to 5th passages (P5). CCK8 and clone formation assay was utilized to assess the proliferation capacity of the chondrocytes. The intracellular Ca2+ and ROS concentrations were evaluated by the Fluo-4-AM Ca2+ probe and DCFH-DA fluorescent probe. beta-Galactosidase staining was used to assess the percentage of senescent cells. The expression of Piezo1, senescence-related and senescence-associated secretory phenotype (SASP)-related genes were detected by real-time quantitative PCR (RT-qPCR) and immunofluorescence. Then, knockdown of Piezo1 in P5 chondrocytes was performed and the above indexes were evaluated. Lastly, P0 chondrocytes were treated with Yoda1 (Piezo1 activator) and BAPTA-AM (Ca2+ chelator) and the above indexes were evaluated. Results: Senescent chondrocytes exhibited intracellular Ca2+ and ROS accumulation. Piezo1 expression levels were increased in senescent chondrocytes and aged mouse cartilage tissue. Knockdown of Piezo1 in P5 chondrocytes reduced Ca2+ and ROS concentrations, promoted the proliferation and reduced the proportion of senescent cells and the expression of SASP-related genes. Activation of Piezo1 in chondrocytes by Yoda1 inhibited the proliferation, promoted senescence and SASP, and increased the concentration of cellular Ca2+ and ROS, but BAPTA-AM intervention reversed these phenomena. Conclusion: This study confirmed for the first time that the high expression of Piezo1 mediated senescence in chondrocytes through Ca2+ accumulation. Piezo1 may be a new target for treating senescence related OA. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

Chondrocyte senescence is closely linked to orthopedic degenerative diseases such as osteoarthritis. This study reveals that the accumulation of calcium ions (Ca2+) plays a role in the aging process of chondrocytes, and the mechanosensitive ion channel Piezo1 is involved in this process through its affinity for Ca2+. The findings suggest that targeting Piezo1 may be a potential therapeutic approach for senescence-related osteoarthritis.