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2022, Vol. 26 ›› Issue (2): 182-189

PDZ domain containing 1 deficiency promotes chondrocyte senescence in osteoarthritis

Guan Hong, Zhang Hongbo, Shao Yan, Guo Dong, Zhang Haiyan, Cai Daozhang   

  1. The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong Province, China

  • Received:2021-01-25 Revised:2021-01-27 Accepted:2021-02-27 Online:2022-01-18 Published:2021-10-27

  • Contact: Cai Daozhang, MD, Chief physician, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong Province, China

  • About author:Guan Hong, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong Province, China

  • Supported by:

    the National Natural Science Foundation of China, No. 81974341 (to CDZ); the Natural Science Foundation of Guangdong Province, No. 2020A1515011062 (to ZHY)



Abstract: BACKGROUND: Osteoarthritis is characterized by the degeneration of articular cartilage. Senescence of chondrocytes, the only type of cells in cartilage, is one of the most important mechanisms of osteoarthritis. However, the specific pathogenesis of osteoarthritis is still unclear. Therefore, we explored the molecular mechanism and signal pathway changes in the disease process and expected to provide new biological targets and research directions for the diagnosis and treatment of osteoarthritis.
OBJECTIVE: To investigate the effect of PDZ domain containing 1 (PDZK1) on chondrocyte senescence in osteoarthritis.
METHODS: (1) Eight-week-old C57 mice were randomly divided into experimental group and sham operation group. Experimental group was then randomly divided into two subgroups of 4 weeks and 8 weeks. In the experimental group, the tibia ligament of the right knee was cut off to dissociate the medial meniscus to induce osteoarthritis. In the sham operation group, only the joint capsule was cut without medial ligament resection and meniscus dissociation. The expression of PDZK1 was detected. (2) The chondrocytes from neonatal mice were isolated by collagenase type II digestion, and cultured. Subsequently, 10 μg/L interleukin-1β was used to stimulate the chondrocytes in order to establish an in vitro cell model of osteoarthritis, and the expression of PDZK1 was knocked down by siRNA-PDZK1. The cells were then divided into untreated group, interleukin 1β treatment group (IL-1β), siRNA-PDZK1 group (si-PD), interleukin 1β and siRNA-PDZK1 co-stimulation group (si-PD+IL-1β). Firstly, we detected the expression of PDZK1 in the chondrocytes. Moreover, chondrocyte formation indicators, such as type II collagen a1, the catabolism indicators, such as matrix metalloproteinase 13, and chondrocyte senescence indicators, including P16, P21, P53, were tested.

RESULTS AND CONCLUSION: Compared with the sham operation group, the expression of PDZK1 was decreased. In the primary chondrocytes of C57/BL6 suckling mice, it was confirmed by western blot that the expression of PDZK1 was decreased significantly in the IL-1β group and si-PD group compared with the untreated group. Furthermore, the expression of type II collagen a1 was reduced markedly in the si-PD group compared with the untreated group. Additionally, the expression of matrix metalloproteinase 13 in si-PD+IL-1β group was increased dramatically compared with the IL-1β group. In the primary chondrocytes of C57/BL6 suckling mice, it was confirmed by real-time fluorescent quantitative PCR that after knocking down the expression of PDZK1 in the si-PD group, the expression of cell senescence indicators, including P16, P21, and P53, were increased significantly compared with the untreated group. These findings indicate that the expression of PDZK1 in chondrocytes is decreased during osteoarthritis progression. PDZK1 deficiency promotes chondrocyte senescence, and exacerbates osteoarthritis. Therefore, PDZK1 may be an important gene that regulates cellular senescence in chondrocytes during the pathogenesis of osteoarthritis, and relevant mechanisms need further studies.

Key words:osteoarthritis, PDZK1, cell senescence, chondrocytes, interleukin-1β


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